ORCID Profile
0000-0001-5391-5069
Current Organisation
Università degli studi di Roma Tor Vergata
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Nanotechnology | Nanomaterials | Nanobiotechnology | Cellular Interactions (incl. Adhesion, Matrix, Cell Wall) | Characterisation of Biological Macromolecules | Nanotechnology | Biomaterials | Colloid And Surface Chemistry | Macromolecular and Materials Chemistry | Synthesis of Materials | Biomechanical Engineering | Biomedical Engineering | Analytical Spectrometry | Nanochemistry and Supramolecular Chemistry | Physical Chemistry Of Macromolecules | Sociology and Social Studies of Science and Technology | Nanomedicine | Immunology | Cellular Immunology | Cell Development, Proliferation and Death
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in Engineering | Other | Workforce Transition and Employment | Organic Industrial Chemicals (excl. Resins, Rubber and Plastics) | Chemical sciences | Physical sciences | Human Pharmaceutical Treatments (e.g. Antibiotics) | Expanding Knowledge in the Physical Sciences | Immune System and Allergy |
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6MH00250A
Abstract: The reactive and oscillating surface of cavitation microbubbles acts as a catalytic binding site for the coupling of hiphilic biomolecules.
Publisher: Wiley
Date: 13-11-2020
Abstract: The manipulation of interfacial properties has broad implications for the development of high-performance coatings. Metal-phenolic networks (MPNs) are an emerging class of responsive, adherent materials. Herein, host-guest chemistry is integrated with MPNs to modulate their surface chemistry and interfacial properties. Macrocyclic cyclodextrins (host) are conjugated to catechol or galloyl groups and subsequently used as components for the assembly of functional MPNs. The assembled cyclodextrin-based MPNs are highly permeable (even to high molecular weight polymers: 250-500 kDa), yet they specifically and noncovalently interact with various functional guests (including small molecules, polymers, and carbon nanomaterials), allowing for modular and reversible control over interfacial properties. Specifically, by using either hydrophobic or hydrophilic guest molecules, the wettability of the MPNs can be readily tuned between superrepellency (>150°) and superwetting (ca. 0°).
Publisher: Wiley
Date: 23-11-2011
Abstract: The assembly of multifunctional nanostructures bearing G-quadruplex motifs broadens the prospects of using G-quadruplexes as therapeutic carriers. Herein, we report the synthesis and characterization of an oligodeoxyguanosine, G15-mer polymer conjugate. We demonstrate that G15-mer oligonucleotides grafted to a polymer chain preserve the ability to self-assemble into ordered structures. The G-quadruplex-polymer conjugates were assembled onto a surface via hybridization with 30-mer cytosine strands, C30-mer, using a layer-by-layer approach to form microcapsules. A mechanism for the sequential assembly of the multilayer films and microcapsules is presented. We further investigate the photophysical behavior of porphyrin TMPyP4 bound to multilayer-coated particles. This study shows that the multilayer films bear residual and functional quadruplex moieties that can be used to effectively bind therapeutic agents.
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1016/S0141-8130(99)00049-5
Abstract: Results of a study on the solution behaviour of the cell-wall polysaccharide named ulvan obtained from hot water extraction of a flour of Ulva 'rigida' are reported. In particular the spectroscopic properties and ion binding capacity of this charged polysaccharide were studied by circular dichroism and isothermal microcalorimetric titrations in order to gain information on the potential exploitation of this low cost biomass. A marked tendency of this polysaccharide to uptake water was evidenced by studying the proton spin-lattice relaxation times of the solvent, T1, embedded in this highly charged polysaccharide.
Publisher: Bentham Science Publishers Ltd.
Date: 08-2010
DOI: 10.2174/156802610791384180
Abstract: Gas-filled microbubbles are widely used in diagnostic imaging. Recent developments have greatly enhanced the potential use of microbubbles for both diagnostic and therapeutic applications. For the potential use of microbubbles in therapeutic applications, the chemical nature of the shell and its mechanical properties are crucial, and requires a tailored synthetic approach. This review describes methods of preparation, mechanism of action, in vitro and in vivo stability and structural/functional characterization of microbubbles. New mechanisms for ultrasound-enhanced local drug and gene delivery are reviewed. Different strategies used to target microbubbles to regions of disease and some of the recent experiences in ultrasound image-guided therapy are discussed.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4RA17109H
Abstract: We report a sonochemical method for the fabrication of stable TiO 2 –chitosan hybrid microspheres possessing nanoporous structure and antimicrobial properties.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2013
DOI: 10.1007/S00216-013-6895-0
Abstract: We report loading of vitamin C (ascorbic acid) on to lysozyme-shelled microbubbles. The interaction between lysozyme-shelled microbubbles and vitamin C was studied by use of cyclic and differential pulse voltammetry, zeta potential measurements, and scanning electron microscopy. The effect of microbubbles on electrochemical measurement of ascorbic acid was evaluated. The linear range for ascorbic acid obtained for differential pulse measurement in the presence of 1 mg mL(-1) microbubbles was 1-50 μmol L(-1) (y = 0.067x + 0.130, r(2) = 0.995), with a detection limit of 0.5 μmol L(-1). The experimental conditions, i.e., pH and ionic strength, were optimized to improve the interaction between ascorbic acid and lysozyme-shelled microbubbles. The results were satisfactory when the interaction was performed for 1 h in aqueous solution at pH 6. The amount of vitamin C loaded on the microbubbles (90% of the analyte added, RSD(inter-expt.) = 3%, n = 6) and the stability of microbubbles-ascorbic acid complex (until 72 h at 25 °C) were also evaluated by use of differential pulse voltammetry and zeta potential measurements.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ULTSONCH.2013.05.004
Abstract: Ultrasonic technique has been used for synthesising protein microspheres possessing specific physical and functional properties. Various proteins have been used as shell materials under different experimental conditions. In previous studies, thermal or chemical denaturation of the proteins was used to obtain stable bovine-serum albumin (BSA) and lysozyme microbubbles (MBs), respectively. It is ideal to establish a generic procedure to synthesise microspheres irrespective of the nature of the protein. In order to see if a generic procedure can be established, ultrasonic synthesis of lysozyme and BSA MBs was carried out under similar experimental conditions and their properties were evaluated. The size, size distribution and the stability of the MBs were significantly different for the lysozyme and BSA MBs. The size and size distribution of the lysozyme coated MBs were larger than BSA bubbles. The mechanical strength of MBs against the shear forces, generated when irradiated by high frequency ultrasound, was studied using pulsed-sonoluminescence (SL). This study indicated that lysozyme MBs were significantly more stable than BSA MBs. An increase in mechanical strength of the MBs may lead to an increase in their storage lifetime and stability against gas diffusion. Possible reasons for such observations have been discussed.
Publisher: Cold Spring Harbor Laboratory
Date: 07-03-2022
DOI: 10.1101/2022.03.07.483273
Abstract: Cardiovascular diseases remain the leading cause of death worldwide hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating and self-organized human cardiac organoids (hCO) in vitro from hiPSCs that can be cultured for long term. This is achieved by differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated human cardiac organoids (hCOs) containing multiple cell types that physiologically compose the heart, gradually self-organize and beat without external stimuli for more than 50 days. We have shown that 3D hCOs display improved cardiac specification, survival and maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hCOs by their response to cardioactive drugs in long term culture. Furthermore, we demonstrated that hCOs can be used to study chemotherapy-induced cardiotoxicity. This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.JHIN.2014.09.009
Abstract: The development of new antimicrobial therapeutic tools addresses the emergence of multidrug-resistant micro-organisms or clones and the need for more effective antimicrobial strategies. Overcoming the hurdles in providing early diagnosis and intervention on hard-to-reach and/or resting bacteria (i.e. biofilm-embedded cells) represents a challenging task. In this review, we identify a set of organic, inorganic, and hybrid materials that might be used for prevention and control of healthcare-associated infections. We report the current knowledge on nano- and microparticle-based antimicrobial agents and describe the possible mode of their action.
Publisher: American Chemical Society (ACS)
Date: 15-04-2008
DOI: 10.1021/CM703702D
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.ULTSONCH.2009.09.012
Abstract: Liquid-encapsulated lysozyme microspheres were successfully synthesized using a sonochemical method. The encapsulation of four different liquids, namely, sunflower oil, tetradecane, dodecane and perfluorohexane on the formation, stability and morphology of the lysozyme microspheres was studied. Among the four different liquids used for encapsulation, perfluorohexane-filled microspheres were found to be most stable in the dried state with a narrow size distribution. In order to explore the possibility of encapsulating biofunctional molecules (e.g., drugs) within these microspheres, liquids containing a fluorescent dye (Nile red) were encapsulated and the ultrasound-induced release of these dye-loaded liquids was studied. The fluorescence data for the liquid-filled lysozyme microspheres demonstrated the potential use of the sonochemical technique for synthesizing these "vehicles" for the encapsulation and the controlled delivery of dyes, flavours, fragrances or drugs.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.BIOADV.2022.213083
Abstract: Glycogen-nucleic acid constructs i.e., glycoplexes are emerging promising platforms for the alteration of gene expression and transcription. Understanding the interaction of glycoplexes with human blood components, such as serum proteins and peripheral blood mononuclear cells (PBMCs), is important to overcome immune cell activation and control biodistribution upon administration of the glycoplexes in vivo. Herein, we investigated the interactions of polyethylene glycol (PEG)ylated and non-PEGylated glycoplexes carrying siRNA molecules with PBMCs isolated from the blood of healthy donors. We found that both types of glycoplexes were non-toxic and were primarily phagocytosed by monocytes without triggering a pro-inflammatory interleukin 6 cytokine production. Furthermore, we investigated the role of the protein corona on controlling the internalization efficiency in immune cells - we found that the adsorption of serum proteins, in particular haptoglobin, alpha-1-antitrypsin and apolipoprotein A-II, onto the non-PEGylated glycoplexes, significantly reduced the uptake of the glycoplexes by PBMCs. Moreover, the non-PEGylated glycoplexes were efficient in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) knockdown in monocytic THP-1 cell line. This study provides an insight into the rational design of glycogen-based nanocarriers for the safe delivery of siRNA without eliciting unwanted immune cell activation and efficient siRNA activity upon its delivery.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0SM00652A
Publisher: American Chemical Society (ACS)
Date: 19-09-2019
Publisher: MDPI AG
Date: 05-10-2023
DOI: 10.3390/NANO13192709
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7NR07814E
Abstract: A dynamic DNA nanoswitch is used to probe NF-κB binding activity and its expression level directly in living cells.
Publisher: Wiley
Date: 2030
Abstract: DNA‐based materials have attracted interest due to the tunable structure and encoded biological functionality of nucleic acids. A simple and general approach to synthesize DNA‐based materials with fine control over morphology and bioactivity is important to expand their applications. Here, we report the synthesis of DNA‐based particles via the supramolecular assembly of tannic acid (TA) and DNA. Uniform particles with different morphologies are obtained using a variety of DNA building blocks. The particles enable the co‐delivery of cytosine‐guanine adjuvant sequences and the antigen ovalbumin in model cells. Intramuscular injection of the particles in mice induces antigen‐specific antibody production and T cell responses with no apparent toxicity. Protein expression in cells is shown using capsules assembled from TA and plasmid DNA. This work highlights the potential of TA as a universal material for directing the supramolecular assembly of DNA into gene and vaccine delivery platforms.
Publisher: Frontiers Media SA
Date: 24-04-2020
Publisher: American Chemical Society (ACS)
Date: 29-06-2002
DOI: 10.1021/MA020134S
Publisher: Wiley
Date: 25-06-2018
Publisher: Elsevier BV
Date: 1997
Publisher: American Chemical Society (ACS)
Date: 15-10-2002
DOI: 10.1021/BM0256247
Abstract: Poly(vinyl alcohol), PVA, is amenable to several structural modifications because of the presence of the hydroxyl moiety in the backbone. The chemical versatility of this polymer can be used for the obtainment of new wall-to-wall pH-responsive PVA chemical hydrogels and for the preparation of air-filled microspheres, for ex le, microbubbles. Here, we report on the characterization of the physical and chemical properties of these novel networks that can be potentially used in different biomedical applications as controlled drug delivery and as ultrasonic contrast agent.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NA00496D
Abstract: Low and high frequency ultrasonic techniques offer a green strategy to synthesize multifunctional nanoparticles from small aromatic biological molecules and proteins with tunable size, morphology, and optical and bio-functional properties.
Publisher: American Chemical Society (ACS)
Date: 07-12-2007
DOI: 10.1021/BM0607269
Abstract: Michael-type addition reactions offer the possibility to obtain in situ formation of polymeric hydrogels in the absence of a radical mechanism for the networking process. We explored such a synthetic route for obtaining a poly(vinyl alcohol) (PVA)-based hydrogel as a potential biomaterial for applications in vitro-retinal replacement surgery. The presence of radicals in the reaction medium can represent a risk for in situ surgical treatment. To circumvent this problem we have applied nucleophilic addition to ad hoc modified PVA macromers. The gel formation has been studied with respect to the timing required in this surgery and in terms of the structural characteristics of the obtained network.
Publisher: Informa UK Limited
Date: 2012
Publisher: MDPI AG
Date: 31-05-2020
DOI: 10.3390/NANO10061075
Abstract: Different polysaccharides—namely dextran, carboxymethyl dextran, alginate, and hyaluronic acid—were compared for the synthesis of nanoporous microsponges particles (NMPs) obtained from a one-pot self-precipitation/cross-linking process. The morphologies and sizes of the NMPs were evaluated comparatively with respect to polymer-to-polymer and cross-linker solvents (water-based vs. DMSO). We found that the radial distribution of the polymer in the near-spherical NMPs was found to peak either at the core or in the corona of the particle, depending both on the specific polymer or the solvent used for the formation of NMPs. The NMP porosity and the swelling capability were evaluated via scanning electron microscopy (SEM). The degradation study indicated that after 10 h incubation with a reducing agent, approximately 80% of the NMPs were disassembled into soluble polysaccharide chains. The adsorption and release capacity of each type of NMP were evaluated using fluorescently labeled bovine serum albumin and lysozyme as model proteins, highlighting a release time typically much longer than the corresponding adsorption time. The dependence of the adsorption-release performance on pH was demonstrated as well. Confocal microscopy images allowed us to probe the different distribution of labeled proteins inside the NMP. The safety and non-cytotoxicity of NMPs were evaluated after incubation with fibroblast 3T3 cells and showed that all types of NMPs did not adversely affect the cell viability for concentrations up to 2.25 μg/mL and an exposure time up to 120 h. Confocal microscopy imaging revealed also the effective interaction between NMPs and fibroblast 3T3 cells. Overall, this study describes a rapid, versatile, and facile approach for preparing a universal non-toxic, nanoporous carrier for protein delivery under physiological conditions.
Publisher: Springer Singapore
Date: 2016
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 12-04-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0CC05095D
Abstract: A one-pot ultrasonic procedure has been developed as a versatile route for synthesizing polymer-coated microspheres that have potential application as drug delivery vehicles. The use of synthetic thiolated poly(methacrylic acid) macromolecules as the shell material offers control over size, morphology and functionality of the microspheres.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BIOMATERIALS.2018.05.024
Abstract: The poor penetration of nanocarrier-siRNA constructs into tumor tissue is a major hurdle for the in vivo efficacy of siRNA therapeutics, where the ability of the constructs to permeate the 3D multicellular matrix is determined by their physicochemical properties. Herein, we optimized the use of soft glycogen nanoparticles for the engineering of glycogen-siRNA constructs that can efficiently penetrate multicellular tumor spheroids and exert a significant gene silencing effect. Glycogen nanoparticles from different bio-sources and with different structural features were investigated. We show that larger glycogen nanoparticles ranging from 50 to 80 nm are suboptimal systems for complexation of nucleic acids if fine control of the size of constructs is required. Our studies suggest that 20 nm glycogen nanoparticles are optimal for complexation and efficient delivery of siRNA. The chemical composition, surface charge, and size of glycogen-siRNA constructs were finely controlled to minimize interactions with serum proteins and allow penetration into 3D multicellular spheroids of human kidney epithelial cells and human prostate cancer cells. We introduced pH sensitive moieties within the construct to enhance early endosome escape and efficiently improve the silencing effect in vitro. Glycogen-siRNA constructs were found to mediate gene silencing in 3D multicellular spheroids causing ∼60% specific gene silencing. The optimized construct exhibited an in vivo circulation lifetime of 8 h in mice, with preferential accumulation in the liver. No accumulation in the kidney, lung, spleen, heart or brain, or signs of toxicity in mice were observed. Our results highlight the potential for screening siRNA nanocarriers in 3D cultured prostate tumor models, thereby improving the predictive therapeutic efficacy of glycogen-based platforms in human physiological conditions.
Publisher: American Chemical Society (ACS)
Date: 29-07-2020
Publisher: Elsevier BV
Date: 06-2021
Publisher: American Chemical Society (ACS)
Date: 06-2210
DOI: 10.1021/JP044807F
Abstract: Molecular dynamics (MD) simulations were carried out to elucidate the dynamic behavior of water confined in poly(vinyl alcohol), PVA, hydrogels. Model topology is supported by experimental network parameters, and simulation results are compared to an incoherent quasielastic neutron scattering (QENS) investigation carried out on PVA hydrogels. From the QENS dynamic scattering law (part I), a random jump model was adopted for the description of water diffusion to extract a microscopic diffusion coefficient and a residence time between two "jumps". In the present work, consistently with this framework, water diffusion parameters as diffusion coefficients and residence times have been evaluated using the mean square displacement of water in a time window of 10 ps and the time autocorrelation function of water hydrogen bonds. The calculated parameters are in good agreement with the experimental ones, giving confidence to this approach. Further developments are in progress to take into account a more realistic description of hydrogel structure in the molecular dynamics simulations.
Publisher: American Chemical Society (ACS)
Date: 23-04-2014
DOI: 10.1021/BM500015J
Abstract: Oil-filled microcapsules of kraft lignin were synthesized by first creating an oil in water emulsion followed by a high-intensity, ultrasound-assisted cross-linking of lignin at the water/oil interface. The rationale behind our approach is based on promoting documented lignin hydrophobic interactions within the oil phase, followed by locking the resulting spherical microsystems by covalent cross-linking using a high intensity ultrasound treatment. As further evidence in support of our rationale, confocal and optical microscopies demonstrated the uniformly spherical morphology of the created lignin microparticles. The detailed elucidation of the cross-linking processes was carried out using gel permeation chromatography (GPC) and quantitative (31)P NMR analyses. The ability of lignin microcapsules to incorporate and release Coumarin-6 was evaluated in detail. In vitro studies and confocal laser scanning microscopy analysis were carried out to assess the internalization of capsules into Chinese hamster ovary (CHO) cells. This part of our work demonstrated that the lignin microcapsules are not cytotoxic and readily incorporated in the CHO cells.
Publisher: American Chemical Society (ACS)
Date: 27-02-2007
DOI: 10.1021/JP0671143
Abstract: A topologically extended model of a chemically cross-linked hydrogel of poly(vinyl alcohol) (PVA) at high hydration degree has been developed for a molecular dynamics simulation with atomic detail at 323 K. The analysis of the 5 ns trajectory discloses structural and dynamic aspects of polymer solvation and elucidates the water hydrogen bonding and diffusion in the network. The features of local polymer dynamics indicate that PVA mobility is not affected by structural constraints of chemical junctions at the investigated cross-linking density, with a prevailing dumping effect due to water interaction. Simulation results are validated by a favorable comparison with findings of an incoherent quasi-elastic neutron scattering study of the same hydrogel system.
Publisher: American Chemical Society (ACS)
Date: 19-01-2006
DOI: 10.1021/BM050723G
Abstract: Hollow (air-filled) microparticles, i.e., microbubbles, provide a promising novel vehicle for both local delivery of therapeutic agents and simultaneous diagnostic ultrasound echo investigations. In this paper, we describe the synthetic routes for decorating the polymeric shell of a poly(vinyl alcohol)-based microbubble with low and high molecular weight ligands with pharmacological relevance. Investigations on physical properties of microbubbles and surface chemical coupling with different cargo molecules such as L-cysteine, L-lysine, poly(L-lysine), chitosan, and beta-cyclodextrin were carried out by CD and NMR spectroscopies, confocal laser scanning microscopy, and microcalorimetry. The in vitro cytotoxicity and biocompatibility of the polymer microbubbles have been also determined toward different cell lines. The results are discussed in terms of the features shown by this device, i.e., injectability, long shelf life, ease of preparation, biocompatibility, loading and cargo capacities, and functional properties.
Publisher: Bentham Science Publishers Ltd.
Date: 16-12-2020
DOI: 10.2174/0929867327666200625151134
Abstract: Nanodrugs represent novel solutions to reshuffle repurposed drugs for cancer therapy. They might offer different therapeutic options by combining targeted drug delivery and imaging in unique platforms. Such nanomaterials are deemed to overcome the limitations of currently available treatments, ultimately improving patients’ life quality. However, despite these promises being made for over three decades, the poor clinical translation of nanoparticle- based therapies calls for deeper in vitro and in vivo investigations. Translational issues arise very early during the development of nanodrugs, where complex and more reliable cell models are often replaced by easily accessible and convenient 2D monocultures. This is particularly true in the field of cancer therapy. In fact, 2D monocultures provide poor information about the real impact of the nanodrugs in a complex living organism, especially given the poor mimicry of the solid Tumors Microenvironment (TME). The dense and complex extracellular matrix (ECM) of solid tumors dramatically restricts nanoparticles efficacy, impairing the successful implementation of nanodrugs in medical applications. Herein, we propose a comprehensive guideline of the 3D cell culture models currently available, including their potential and limitations for the evaluation of nanodrugs activity. Advanced culture techniques, more closely resembling the physiological conditions of the TME, might give a better prediction of the reciprocal interactions between cells and nanoparticles and eventually help reconsider the use of old drugs for new applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B618779J
Publisher: American Chemical Society (ACS)
Date: 06-08-2020
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2023
DOI: 10.1101/2023.03.10.532035
Abstract: Interactions between living cells and nanoparticles have been extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness and surface charge have been regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigated the role of cellular mechanosensitive components in cell-nanoparticle interactions. We demonstrate that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, we propose targeting YAP may sensitize triple negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.
Publisher: American Academy of Pediatrics (AAP)
Date: 05-2012
Abstract: Sweet syndrome is an inflammatory disease characterized by fever and painful erythematous plaques with a dermal neutrophilic infiltrate. It is most common in adults, where it is often parainflammatory or paraneoplastic, but is rare in children. We describe 3 cases of neonatal Sweet syndrome, including 1 patient who had myelodysplastic syndrome and immunodeficiency, the first report of a premalignancy underlying infantile Sweet syndrome. We reviewed the literature on patients presenting with neutrophilic dermatosis in the first 6 months of life. Of 20 cases, 6 had a probable viral etiology, 4 primary immunodeficiencies, 3 neonatal lupus syndrome, 1 gastrointestinal involvement, 1 HIV, and 5 probable genetic cases. Three of these had chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome, caused by mutations in the PSMB8 gene. Most children who presented within the first 6 weeks of life had either a serious underlying condition, such as primary immunodeficiency, or a genetic Sweet syndrome, with 2 fatalities among this latter group. The outcome of postinfective cases was good. Extracutaneous involvement was unusual, whereas postinflammatory scarring and cutis laxa occurred in a minority of patients. In conclusion, Sweet syndrome in the neonatal period often heralds a serious underlying disorder and requires thorough investigation.
Publisher: Wiley
Date: 31-07-2006
Abstract: Polysaccharide hydrogels have found several applications in the food industry, in biomedicine, and cosmetics. The study of polysaccharide hydrogels offers a challenging scenario of intrinsic heterogeneities in the crosslinking density and large time and space ranges that characterize a number of dynamic processes entailing segmental motions, water diffusion, and small-molecule diffusion. The understanding of such complex features is essential because of the extensive use of polysaccharidic moieties in the food industry, biomedical devices, and cosmetics. The study of phenomena occurring at the nanoscale to the mesoscale requires the combination of investigative tools to probe different time and distance scales and the structural characterization of the networks by established methodologies such as swelling and elastic modulus measurements. Elastic and quasielastic neutron scattering, and fluorescence recovery after photobleaching are emerging methodologies in this field. In this feature article we focus, somewhat arbitrarily, on these new approaches because other techniques, such as low-resolution proton NMR relaxometry and rheology, have been already described thoroughly in the literature. Case ex les of polysaccharide hydrogels studied by neutron scattering and fluorescence recovery are presented here as contributions to the comprehension of the dynamic behavior of physical and chemical hydrogels based on polysaccharides. Quasielastic incoherent neutron scattering experiment on a Sephadex hydrogel s le at different temperatures.
Publisher: Wiley
Date: 13-11-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NR08429A
Abstract: Nanocomplexes of glycogen nanoparticles with serum albumin were formed by triggering the nanophase separation of albumin. The nanocomplexes enabled the delivery of chemotherapeutics in complex multicellular 3D tumour-like structures.
Publisher: American Chemical Society (ACS)
Date: 03-09-2004
DOI: 10.1021/BM049654G
Abstract: The need of innovative, multifunctional biomaterials for the partial or complete tissue replacement is the driving force for the search of improvements of the performances of the available materials and in the formulation of new ones. Addressing the focus to vitreous substitution, we have explored the possibility of using injectable aqueous solutions of poly(vinyl alcohol), PVA, derivatives able to form hydrogels in the ocular cavity upon UV-vis irradiation with visible light. In particular, we describe the features of hydrogels from methacrylate grafted PVA, PVA-MA, in terms of structural characteristics, degradation processes, release of low- and high- molecular weight molecules, and in vitro gelation kinetics. The mechanical properties, drug delivery tests, and rheology tests suggest that PVA-MA derivatives have the potential to become a useful material for vitreous substitution.
Publisher: MDPI AG
Date: 07-12-2016
DOI: 10.3390/GENES7120119
Publisher: American Chemical Society (ACS)
Date: 08-10-2021
Publisher: Wiley
Date: 16-10-2020
Abstract: Biological nanoparticles found in living systems possess distinct molecular architectures and erse functions. Glycogen is a unique biological polysaccharide nanoparticle fabricated by nature through a bottom-up approach. The biocatalytic synthesis of glycogen has evolved over time to form a nanometer-sized dendrimer-like structure (20-150 nm) with a highly branched surface and a dense core. This makes glycogen markedly different from other natural linear or branched polysaccharides and particularly attractive as a platform for biomedical applications. Glycogen is inherently biodegradable, nontoxic, and can be functionalized with erse surface and internal motifs for enhanced biofunctional properties. Recently, there has been growing interest in glycogen as a natural alternative to synthetic polymers and nanoparticles in a range of applications. Herein, the recent literature on glycogen in the material-based sciences, including its use as a constituent in biodegradable hydrogels and fibers, drug delivery vectors, tumor targeting and penetrating nanoparticles, immunomodulators, vaccine adjuvants, and contrast agents, is reviewed. The various methods of chemical functionalization and physical assembly of glycogen nanoparticles into multicomponent nanodevices, which advance glycogen toward a functional therapeutic nanoparticle from nature and back again, are discussed in detail.
Publisher: No publisher found
Date: 2013
DOI: 10.1021/AM302660J
Abstract: Air-filled lysozyme microbubbles (LSMBs) were engineered as a support for the immobilization of gold nanoparticles and an enzyme, alkaline phosphatase, in order to develop micro-antimicrobial and biosensing devices. Gold nanoparticles immobilized on LSMBs significantly improved the antimicrobial efficacy of the microbubbles against M. lysodeikticus. The surface functionalization of the microbubbles with gold nanoparticles did not affect their echogenicity when exposed to an ultrasound imaging probe. Alkaline phosphatase was conjugated on the surface of microbubbles without compromising its enzymatic activity. The functionalized microbubbles were used for the detection of paraoxon in aqueous solutions.
Publisher: Wiley
Date: 28-09-2020
Publisher: Wiley
Date: 02-2006
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7GC03163G
Abstract: A sustainable, reagent-less and one-pot ultrasonic methodology has been developed to transform amorphous tannic acid into regularly shaped crystalline ellagic acid particles.
Publisher: American Chemical Society (ACS)
Date: 24-08-2023
Publisher: American Chemical Society (ACS)
Date: 02-06-2015
Abstract: An oil-in-water emulsion was ultrasonically prepared in aqueous chitosan solutions containing different counterions. Tetradecane was used as the oil phase in order to mimic nonpolar substances used in food processes. Various acids were used to dissolve chitosan, and we found that conjugate bases of the acids used, which act as counterions to neutralize the positive charges of ammonium ions present in the chitosan backbone, played a significant role in controlling the size, size distribution, and stability of chitosan-encapsulated tedradecane emulsion droplets (microspheres). The counterion effect is also found to be strongly dependent upon tetradecane (TD)/chitosan (CS) ratio and ultrasonic power. Key observations are: (i) for a given TD/CS ratio, the size and size distribution decrease when the acid is varied from nitric acid to benzenesulfonic acid at high TD/CS ratio, and the effect becomes less significant at low TD/CS ratio (ii) for a given acid, the size and size distribution increase with an increase in TD/CS ratio and (iii) at low TD/CS ratio the size and size distribution are significantly influenced by the viscosity of the system. A possible mechanism for the observed counterion effect is proposed. The role of counterions, solution viscosity, and ultrasonic power in controlling the physical and functional properties of ultrasonically generated chitosan-stabilized tetradecane microspheres is discussed in detail. The key new finding of this study is that it is possible to form stable emulsions without the addition of external emulsifiers and stabilizers, but only using chitosan with different acids to dissolve chitosan. This strategy could be used in the generation of stable food emulsions.
Publisher: Springer Singapore
Date: 2015
Publisher: Bentham Science Publishers Ltd.
Date: 04-2006
DOI: 10.2174/138161206776361138
Abstract: In recent years pharmaceutical design has been facing the needs expressed by new therapeutic methodologies such as gene therapy, targeted delivery and closely related diagnostic fields as contrast enhancing agents for ultrasonic investigations. In this context pharmaceutical research has ersified the efforts toward a more integrated approach where the efficacy of an active molecule is enhanced and assisted by the surrounding carrier. Usually this drug platform is a hydrogel matrix, a multicomponent system constituted by an aqueous solution and a polymeric moiety imparting different functions to the matrix, as responsiveness to external stimuli, affinity to receptors, controlled drug release. Such devices represent one of the leading topics of the soft condensed matter recent research, a domain where physics, chemistry and bioengineering cross each other with the aim to achieve an integrated description of these materials. In this respect modern drug design will make use more and more of concepts proper of soft condensed polymer and colloidal sciences. In this review we will describe the state-of-art in the field of the matrices used in innovative drug formulations with a particular emphasis on the implications to pharmaceutical design along with the experimental and theoretical investigation tools worked out in the last decade.
Publisher: American Chemical Society (ACS)
Date: 11-08-2005
DOI: 10.1021/LA050287J
Abstract: Gas filled hollow microparticles, i.e., microbubbles and microballoons, are soft matter devices used in a number of erse applications ranging from protein separation and purification in food science to drilling technology and ultrasound imaging. Aqueous dispersions of these mesoscopic systems are characterized by the stabilization of the air/water interface by a thin shell of phospholipid bilayer or multilayers or by a denatured and cross-linked proteic matrix. We present a study of a type of microballoons based on modified poly(vinyl alcohol), PVA, a synthetic biocompatible polymer, with new structural features. A cross-linking reaction carried out at the air/water interface provides polymeric air-filled microbubbles with average dimensions depending on the reaction temperature. Characterization of diameters and shell thicknesses for microbubbles obtained at different temperatures has been carried out. Conversion to solvent-filled hollow microcapsules is possible by soaking microbubbles in dimethyl sulfoxide. Microcapsules permeability to fluorescent labeled dextran molecular weight standards was correlated to the mesh size of the polymer network of the shell. Microbubbles were covalently grafted under very mild conditions with beta-cyclodextrin and poly-l-lysine with a view to assay the capability of the device for delivery of hydrophobic drugs or DNA. PVA based microballoons show a remarkable shelf life of several months, their external surface can be decorated with many biologically relevant molecules. These features, together with a tested biocompatibility, make them attractive candidates for use as multifunctional device for diagnosis and therapeutic purposes, i.e., as ultrasound reflectors in ecographic investigation and as drug platforms for in situ sonoporation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3MA00137G
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NR08418F
Abstract: A chimeric locked nucleic acid (LNA)–DNA sensor enables hybridization chain reaction (HCR) for the efficient detection and nanoscale imaging of HIV-1 RNA transcripts in cell lysates, and fixed and live cells.
Publisher: Wiley
Date: 29-08-2018
Abstract: Interfacial self-assembly is a powerful organizational force for fabricating functional nanomaterials, including nanocarriers, for imaging and drug delivery. Herein, the interfacial self-assembly of pH-responsive metal-phenolic networks (MPNs) on the liquid-liquid interface of oil-in-water emulsions is reported. Oleic acid emulsions of 100-250 nm in diameter are generated by ultrasonication, to which poly(ethylene glycol) (PEG)-based polyphenolic ligands are assembled with simultaneous crosslinking by metal ions, thus forming an interfacial MPN. PEG provides a protective barrier on the emulsion phase and renders the emulsion low fouling. The MPN-coated emulsions have a similar size and dispersity, but an enhanced stability when compared with the uncoated emulsions, and exhibit a low cell association in vitro, a blood circulation half-life of ≈50 min in vivo, and are nontoxic to healthy mice. Furthermore, a model anticancer drug, doxorubicin, can be encapsulated within the emulsion phase at a high loading capacity (≈5 fg of doxorubicin per emulsion particle). The MPN coating imparts pH-responsiveness to the drug-loaded emulsions, leading to drug release at cell internalization pH and a potent cell cytotoxicity. The results highlight a straightforward strategy for the interfacial nanofabrication of pH-responsive emulsion-MPN systems with potential use in biomedical applications.
Publisher: MDPI AG
Date: 25-08-2021
DOI: 10.3390/MOLECULES26175157
Abstract: Ultrasonically synthesized core-shell microcapsules can be made of synthetic polymers or natural biopolymers, such as proteins and polysaccharides, and have found applications in food, drug delivery and cosmetics. This study reports on the ultrasonic synthesis of microcapsules using unmodified (natural) and biodegradable glycogen nanoparticles derived from various sources, such as rabbit and bovine liver, oyster and sweet corn, for the encapsulation of soybean oil and vitamin D. Depending on their source, glycogen nanoparticles exhibited differences in size and ‘bound’ proteins. We optimized various synthetic parameters, such as ultrasonic power, time and concentration of glycogens and the oil phase to obtain stable core-shell microcapsules. Particularly, under ultrasound-induced emulsification conditions (sonication time 45 s and sonication power 160 W), native glycogens formed microcapsules with diameter between 0.3 μm and 8 μm. It was found that the size of glycogen as well as the protein component play an important role in stabilizing the Pickering emulsion and the microcapsules shell. This study highlights that native glycogen nanoparticles without any further tedious chemical modification steps can be successfully used for the encapsulation of nutrients.
Publisher: MDPI AG
Date: 08-09-2020
DOI: 10.3390/NANO10091772
Abstract: High-frequency ultrasound treatment is found to be a one-pot green technique to produce peptide-based nanostructures by ultrasound assisted self-assembly of oligopeptides. [Arg-Phe]4 octapeptides, consisting of alternating arginine (Arg/R) and phenylalanine (Phe/F) sequences, were subjected to 430 kHz ultrasound in aqueous solution in the absence of any external agents, to form [RF]4 nanoparticles ([RF]4-NPs), ~220 nm in diameter. A comprehensive analysis of the obtained nanoparticles demonstrated that the aromatic moieties of the oligopeptides can undergo oxidative coupling to form multiple oligomeric species, which then self-assemble into well-defined fluorescent nanoparticles. [RF]4-NPs were functionalized with polyethylene glycol (PEGylated) to improve their colloidal stability. Unlike the parent peptide, the PEGylated [RF]4-NPs showed limited cytotoxicity towards MDA-MB-231 cells. Furthermore, the intracellular trafficking of PEGylated [RF]4-NPs was investigated after incubation with MDA-MB-231 cells to demonstrate their efficient endo-lysosomal escape. This work highlights that the combined use of ultrasonic technologies and peptides enables easy fabrication of nanoparticles, with potential application in drug delivery.
Publisher: Cold Spring Harbor Laboratory
Date: 28-08-2021
DOI: 10.1101/2021.08.27.457906
Abstract: Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by re-expressing fetal contractile proteins via transcriptional and post-transcriptional processes, like alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is upregulated and relocates to the sarcomeric Z-disk upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates to the translation machinery. Alterations in hnRNPC expression and localization can be mechanically determined and affect the AS of numerous mRNAs involved in mechanotransduction and cardiovascular diseases, like Hippo pathway effector YAP1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by impacting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNAs homeostasis mechanoregulation in pathological conditions.
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Chemical Society (ACS)
Date: 21-06-2012
DOI: 10.1021/MZ3002534
Abstract: We report a novel flow-through sonication technique for synthesizing stable and monodispersed nano- and micrometer-sized bubbles that have potential applications in diagnostics and gene therapy. The size and size distribution of the bubbles are controlled by the active cavitation zone generated by ultrasound. These bubbles are shown to possess echogenic properties and can be used for loading oligonucleotides.
Publisher: American Chemical Society (ACS)
Date: 29-11-2022
Abstract: Metal-phenolic networks (MPNs) are amorphous materials that can be used to engineer functional films and particles. A fundamental understanding of the heat-driven structural reorganization of MPNs can offer opportunities to rationally tune their properties ( e . g ., size, permeability, wettability, hydrophobicity) for applications such as drug delivery, sensing, and tissue engineering. Herein, we use a combination of single-molecule localization microscopy, theoretical electronic structure calculations, and all-atom molecular dynamics simulations to demonstrate that MPN plasticity is governed by both the inherent flexibility of the metal (Fe III )-phenolic coordination center and the conformational elasticity of the phenolic building blocks (tannic acid, TA) that make up the metal-organic coordination complex. Thermal treatment (heating to 150 °C) of the flexible TA/Fe III networks induces a considerable increase in the number of aromatic π-π interactions formed among TA moieties and leads to the formation of hydrophobic domains. In the case of MPN capsules, 15 min of heating induces structural rearrangements that cause the capsules to shrink (from ∼4 to ∼3 μm), resulting in a thicker (3-fold), less porous, and higher protein ( e.g. , bovine serum albumin) affinity MPN shell. In contrast, when a simple polyphenol such as gallic acid is complexed with Fe III to form MPNs, rigid materials that are insensitive to temperature changes are obtained, and negligible structural rearrangement is observed upon heating. These findings are expected to facilitate the rational engineering of versatile TA-based MPN materials with tunable physiochemical properties for erse applications.
Publisher: Wiley
Date: 06-08-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4NR07240E
Abstract: Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMA(SH) triggers cell defense responses erturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMA(SH) into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMA(SH)) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMA(SH) polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association.
Publisher: Elsevier BV
Date: 05-2022
Publisher: American Chemical Society (ACS)
Date: 21-06-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B715392A
Publisher: American Chemical Society (ACS)
Date: 19-08-2008
DOI: 10.1021/LA801093Q
Abstract: High-intensity ultrasound induces emulsification and cross-linking of protein molecules in aqueous medium. The stability and the functionality of the resultant protein-coated microbubbles are crucial in many of their applications. For ex le, the stability of drug-loaded microbubbles should be sufficiently long enough, in vivo, so that they can be ruptured only at specific sites for release of the drugs. In this study, we report the synthesis of stable and functional microbubbles, coated with chemically reduced lysozyme, using high-intensity ultrasound in aqueous solution. In the absence of chemical reduction, stable microbubbles were not produced with native lysozyme, indicating the importance of free -SH functional groups for protein cross-linking. The degree of cross-linking between lysozyme molecules was controlled by manipulating both the extent of chemical reduction of the intramolecular disulfide bonds and sonication time. The lysozyme-coated microbubbles are stable for several months and retain the enzymatic (antimicrobial) activity of lysozyme. The layer-by-layer (LbL) deposition of polyelectrolytes onto the protein-shell air-core template has been used as a versatile procedure to modify the surface properties of the microbubbles, indicating the possibility of adsorbing potential drugs and/or biolabels on the surface of these microbubbles for therapeutic and diagnostic applications.
Publisher: Elsevier BV
Date: 02-2001
Publisher: Informa UK Limited
Date: 19-04-2011
DOI: 10.1080/08927014.2011.565123
Abstract: The present work reports on the first attempt to study water mobility in phototrophic biofilms, applying the (1)H-NMR relaxometry technique to closely monitored microbial communities grown in a microcosm under controlled ambient conditions. Longitudinal water proton relaxation times exhibited a bi-exponential behavior in all biofilm s les, indicating two types of water molecules with erging dynamic properties, confined to different compartments of the biofilm. The fast-relaxing component can be attributed to water molecules tightly bound to the intracellular matrix, while the slow-relaxing component could reflect the behavior of water embedded in the biopolymer matrix, confined into matrix pores and channels. The results are discussed with respect to a possible key role of exopolysaccharides and uronic acids in water binding in phototrophic biofilms.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0TB00299B
Abstract: Amphiphilic phytoglycogen nanoparticles are used as building blocks for engineering multifunctional hybrid films with catalytic and sensing properties.
Publisher: Wiley
Date: 09-09-2003
DOI: 10.1002/APP.12829
Publisher: American Chemical Society (ACS)
Date: 06-06-2008
DOI: 10.1021/BM800225V
Abstract: Micro- and nanoparticles are considered suitable drug delivery systems for their unique features, such as a large surface to volume ratio, and for the possibility to tune their size and hydrophobicity. A polymer olymer/water emulsion method was used for producing a chemically cross-linked hydrogel made of poly(vinyl alcohol) and of poly(methacrylate) moieties. Mesoscopic investigation of the microparticles was accomplished by laser scanning confocal microscopy. Dynamics of confined water within the gel meshes was studied by quasi-elastic incoherent neutron scattering. Succinoylation of these particles allowed an efficient loading with a maximum doxorubicin payload of about 50% (w/w) of dry microparticles. To evaluate the potentials of such a microdevice for drug delivery, LoVo colon cancer cells have been exposed to doxorubicin loaded microparticles to study the in vitro efficiency of the payload release and the consequent cytotoxic effect.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2012
DOI: 10.1007/S00726-011-1148-Z
Abstract: Microbubbles (MBs) have specific acoustic properties that make them useful as contrast agents in ultrasound imaging. The use of the MBs in clinical practice led to the development of more sensitive imaging techniques both in cardiology and radiology. Protein-MBs are typically obtained by dispersing a gas phase in the protein solution and the protein deposited/cross-linked on the gas-liquid interface stabilizes the gas core. Innovative applications of protein-MBs prompt the investigation on the properties of MBs obtained using different proteins that are able to confer them specific properties and functionality. Recently, we have synthesized stable air-filled lysozyme-MBs (LysMBs) using high-intensity ultrasound-induced emulsification of a partly reduced lysozyme in aqueous solutions. The stability of LysMBs suspension allows for post-synthetic modification of MBs surface. In the present work, the protein folded state and the biodegradability property of LysMBs were investigated by limited proteolysis. Moreover, LysMBs were coated and functionalized with a number of biomacromolecules (proteins, polysaccharides, nucleic acids). Remarkably, LysMBs show a high DNA-binding ability and protective effects of the nucleic acids from nucleases and, further, the ability to transform the bacteria cells. These results highlight on the possibility of using LysMBs for delivery of proteins and nucleic acids in prophylactic and therapeutic applications.
Publisher: Elsevier BV
Date: 04-1998
Publisher: American Chemical Society (ACS)
Date: 19-12-2019
Abstract: The intracellular delivery of nucleic acids and proteins remains a key challenge in the development of biological therapeutics. In gene therapy, the inefficient delivery of small interfering RNA (siRNA) to the cytosol by lipoplexes or polyplexes is often ascribed to the entrapment and degradation of siRNA payload in the endosomal compartments. A possible mechanism by which polyplexes rupture the endosomal membrane and release their nucleic acid cargo is commonly defined as the "proton sponge effect". This is an osmosis-driven process triggered by the proton buffering capacity of polyplexes. Herein, we investigate the molecular basis of the "proton sponge effect" through direct visualization of the siRNA trafficking process, including analysis of in idual polyplexes and endosomes, using stochastic optical reconstruction microscopy. We probe the sequential siRNA trafficking steps through single molecule super-resolution analysis of subcellular structures, polyplexes, and silencing RNA molecules. Specifically, in idual intact polyplexes released in the cytosol upon rupture of the endosomes, the damaged endosomal vesicles, and the disassembly of the polyplexes in the cytosol are examined. We find that the architecture of the polyplex and the rigidity of the cationic polymer chains are crucial parameters that control the mechanism of endosomal escape driven by the proton sponge effect. We provide evidence that in highly branched and rigid cationic polymers, such as glycogen or polyethylenimine, immobilized on silica nanoparticles, the proton sponge effect is effective in inducing osmotic swelling and rupture of endosomes.
Publisher: Wiley
Date: 16-10-2018
Publisher: Elsevier BV
Date: 05-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6CC08607A
Abstract: Flavonoid films: dietary flavonoids assemble into biofunctional films and capsules in a one-step process via metal coordination. The antioxidant property of the parent flavonoid is enhanced when assembled into a film and can be reused over multiple cycles.
Publisher: Elsevier BV
Date: 07-2004
Publisher: Wiley
Date: 25-04-2019
Publisher: Author(s)
Date: 2016
DOI: 10.1063/1.4954496
Publisher: Wiley
Date: 10-02-2023
Abstract: DNA‐based materials have attracted interest due to the tunable structure and encoded biological functionality of nucleic acids. A simple and general approach to synthesize DNA‐based materials with fine control over morphology and bioactivity is important to expand their applications. Here, we report the synthesis of DNA‐based particles via the supramolecular assembly of tannic acid (TA) and DNA. Uniform particles with different morphologies are obtained using a variety of DNA building blocks. The particles enable the co‐delivery of cytosine‐guanine adjuvant sequences and the antigen ovalbumin in model cells. Intramuscular injection of the particles in mice induces antigen‐specific antibody production and T cell responses with no apparent toxicity. Protein expression in cells is shown using capsules assembled from TA and plasmid DNA. This work highlights the potential of TA as a universal material for directing the supramolecular assembly of DNA into gene and vaccine delivery platforms.
Publisher: Elsevier BV
Date: 07-2001
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.CARRES.2005.01.023
Abstract: Proton fluctuations reporting local motions of the glycosidic linkages of chemically crosslinked dextran hydrogels with well defined pore-size distributions are studied by static and dynamic neutron-scattering approaches. The dependence of the dynamic behaviour of water on the pore sizes is also discussed.
Publisher: Elsevier BV
Date: 05-1997
DOI: 10.1016/S0008-6215(97)00023-2
Abstract: The results of measurements of longitudinal and transverse proton relaxation times for a chemical network obtained by reacting chitosan with oxidized beta-cyclodextrin (beta-cyclodextrin polyaldehyde) are presented. The network was characterized by a 'two-component' transverse relaxation mechanism relative to structurally different environments experienced by water molecules. Different environments were also indicated by the temperature of the spin-spin relaxation times (T2) studied in the range 4-50 degrees C. Between 4 and 18 degrees C, proton exchange between the matrix and water prevails on the inter- and intra-molecular dipolar interactions of the water confined in the meshes of the network, resulting in a marked change in the slope of T2 with temperature. Stiffness of the matrix and reduced mobility of water in the gel meshes are prerequisites for observing such relaxation phenomena. Possible mechanisms contributing to the activation energy in the case of chitosan-cyclodextrin networks are discussed. The behaviour of the chitosan-cyclodextrin hydrogel is compared with that of a gellan gel.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6TB02105K
Abstract: Polymer carriers induce assembly of drugs into nanoaggregates and play a role in tuning the architecture and bioactivity of drug nanoaggregates.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9NH00611G
Abstract: The out-of-equilibrium self-assembly of simple aromatic amino acid molecules is driven by high frequency ultrasound, where acoustic energy acts as a fuel to form uniform supramolecular nanostructures with multifarious optical and biological properties.
Publisher: American Chemical Society (ACS)
Date: 08-12-2001
DOI: 10.1021/MA001076I
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0NR03087B
Abstract: The intracellular interactions and fate of a DNA nanosensor were investigated by combining quantitative microscopy and stochastic optical reconstruction microscopy.
Publisher: American Chemical Society (ACS)
Date: 14-05-2019
DOI: 10.1021/ACS.LANGMUIR.9B00896
Abstract: This feature article provides a review of recent work on the synthesis of biopolymer-shelled microbubbles using various techniques with a particular focus on ultrasonic methodology that offers advantages over other conventional methods for tuning their physical and functional properties. A detailed discussion on the role of surface chemistry in fabricating functional lysozyme-shelled microbubbles has also been presented. Highlights on the applications of lysozyme-shelled microbubbles, particularly recent findings on their use for potential theranostic applications in lung diseases, have also been presented.
Publisher: Wiley
Date: 24-04-2013
Publisher: American Chemical Society (ACS)
Date: 29-06-2015
DOI: 10.1021/ACS.BIOMAC.5B00562
Abstract: We report the engineering of intracellular redox-responsive nanoporous poly(ethylene glycol)-poly(l-lysine) particles (NPEG-PLLs). The obtained particles exhibit no toxicity while maintaining the capability to deliver a small interfering RNA sequence (siRNA) targeting the anti-apoptotic factor, survivin, in prostate cancer cells. The redox-mediated cleavage of the disulfide bonds stabilizing the NPEG-PLL-siRNA complex results in the release of bioactive siRNA into the cytosol of prostate cancer PC-3 cells, which, in turn, leads to the effective silencing (∼59 ± 8%) of the target gene. These findings, obtained under optimal conditions, indicate that NPEG-PLLs may protect the therapeutic nucleic acid in the extracellular and intracellular environments, thus preventing the occurrence of competitive interactions with serum and cytosolic proteins as well as degradation by RNase. The intracellular trafficking and final fate of the NPEG-PLLs were investigated by a combination of deconvolution microscopy, fluorescence lifetime imaging microscopy, and super-resolution structured illumination microscopy. A significant impairment of cell survival was observed in cells concomitantly exposed to paclitaxel and siRNA-loaded NPEG-PLLs. Overall, our findings indicate that NPEG-PLLs represent a highly loaded depot for the delivery of therapeutic nucleic acids to cancer cells.
Publisher: Springer Singapore
Date: 2016
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JCCT.2016.12.007
Abstract: Epicardial adipose tissue (EAT) is a metabolically active fat depot that is associated with incident coronary artery disease (CAD) and major adverse cardiovascular events. The relationship between EAT and myocardial ischemia remains unclear. This study investigated the relationship between EAT volume and the presence of perfusion defects on myocardial computed tomographic perfusion imaging (CTP) and functional stenoses on invasive fractional flow-reserve (FFR). Data were obtained from a previous prospective cross-sectional study in patients with suspected CAD. Patients underwent combined coronary computed tomography angiography (coronary CTA) and CTP followed by invasive coronary angiogram (ICA) and FFR within 14 days. FFR was performed in all major epicardial vessels unless they were angiographically smooth or occluded, with a threshold of <0.8 considered significant. EAT volume was quantified semi-automatically on coronary CTA. There were 38 patients included for analysis, mean age 62.5 ± 10.0 years, 68.4% male. Median EAT volume was 82.8 mL (interquartile range (IQR) 49.3 mL). FFR was interrogated in 73/114 (64%) vessels. There was no difference in EAT volumes in patients with and without CTP defects (84.4 mL, IQR: 35.6 mL vs 81.1 mL, IQR: 53.1 mL, p = 0.7). There was also no difference in EAT volumes in patients with and without FFR-significant vessels (86.5 mL IQR: 36.6 mL vs 79.1 mL IQR: 54.5 mL, p = 0.7) and no difference when analysed by number of CTP positive territories or FFR-significant vessels (p = 0.4 and p = 0.8 respectively). This study demonstrated no observable relationship between EAT volume and perfusion defects on myocardial CT perfusion imaging or functional stenosis on invasive FFR.
Publisher: Wiley
Date: 12-03-2023
Abstract: Glucose‐responsive insulin‐delivery platforms that are sensitive to dynamic glucose concentration fluctuations and provide both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. Here, biodegradable and charge‐switchable phytoglycogen nanoparticles capable of glucose‐stimulated insulin release are engineered. The nanoparticles are “nanosugars” bearing glucose‐sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nanocomplexes. A single subcutaneous injection of nanocomplexes shows a rapid and efficient response to a glucose challenge in two distinct diabetic mouse models, resulting in optimal blood glucose levels (below 200 mg dL –1 ) for up to 13 h. The morphology of the nanocomplexes is found to be key to controlling rapid and extended glucose‐regulated insulin delivery in vivo. These studies reveal that the injected nanocomplexes enabled efficient insulin release in the mouse, with optimal bioavailability, pharmacokinetics, and safety profiles. These results highlight a promising strategy for the development of a glucose‐responsive insulin delivery system based on a natural and biodegradable nanosugar.
Publisher: American Chemical Society (ACS)
Date: 13-11-2018
Abstract: Nanostructured materials have potential as platforms for analytical assays and catalytic reactions. Herein, we report the synthesis of electrocatalytically active cobalt phosphate nanostructures (CPNs) using a simple, low-cost, and scalable preparation method. The electrocatalytic properties of CPNs toward the electrooxidation of glucose (Glu) were studied by cyclic voltammetry and chrono erometry in relevant biological electrolytes, such as phosphate-buffered saline (PBS), at physiological pH (7.4). Using CPNs, Glu detection could be achieved over a wide range of biologically relevant concentrations, from 1 to 30 mM Glu in PBS, with a sensitivity of 7.90 nA/mM cm
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.ULTSONCH.2020.104967
Abstract: A simple, one-pot high frequency ultrasonication (490 kHz) methodology to convert hydrophobic and hipathic amino acids into nanostructures was investigated. The approach involved the oxidative coupling of aromatic amino acids (phenylalanine and tryptophan) in aqueous solutions to form high molecular weight dimers and oligomers. The role of cavitation bubble surface and ultrasonic power to trigger the out-of-equilibrium self-assembly of dimers and trimers to spherical and uniform nanostructures with controlled size has been discussed. The synthesized particles exhibited fluorescence in blue, green and red spectral regions and a strong antioxidant activity.
Publisher: Wiley
Date: 10-06-2022
DOI: 10.1002/PSC.3356
Abstract: Synthetic therapeutic peptides (STP) are intensively studied as new‐generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico‐chemical properties of the active principle. The aggregation properties of a 20‐mer STP (Ac‐His‐Ala‐Arg‐Ile‐Lys‐D‐Pro‐Thr‐Phe‐Arg‐Arg‐D‐Leu‐Lys‐Trp‐Lys‐Tyr‐Lys‐Gly‐Lys‐Phe‐Trp‐NH 2 ), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H‐460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution.
Publisher: Wiley
Date: 18-02-2022
Abstract: Reconfiguring the structure and selectivity of existing chemotherapeutics represents an opportunity for developing novel tumor‐selective drugs. Here, as a proof‐of‐concept, the use of high‐frequency sound waves is demonstrated to transform the nonselective anthracycline doxorubicin into a tumor selective drug molecule. The transformed drug self‐aggregates in water to form ≈200 nm nanodrugs without requiring organic solvents, chemical agents, or surfactants. The nanodrugs preferentially interact with lipid rafts in the mitochondria of cancer cells. The mitochondrial localization of the nanodrugs plays a key role in inducing reactive oxygen species mediated selective death of breast cancer, colorectal carcinoma, ovarian carcinoma, and drug‐resistant cell lines. Only marginal cytotoxicity (80–100% cell viability) toward fibroblasts and cardiomyocytes is observed, even after administration of high doses of the nanodrug (25–40 µg mL −1 ). Penetration, cytotoxicity, and selectivity of the nanodrugs in tumor‐mimicking tissues are validated by using a 3D coculture of cancer and healthy cells and 3D cell‐collagen constructs in a perfusion bioreactor. The nanodrugs exhibit tropism for lung and limited accumulation in the liver and spleen, as suggested by in vivo biodistribution studies. The results highlight the potential of this approach to transform the structure and bioactivity of anticancer drugs and antibiotics bearing sono‐active moieties.
Publisher: Bentham Science Publishers Ltd.
Date: 03-2012
DOI: 10.2174/138161212800099874
Abstract: Microbubbles (MBs) are ultrasound responsive colloidal particles with a strong potential to become theranostic agents, combining the contrast agent activity with therapeutic functionality. In the last decades, MBs have played a significant role as ultrasound contrast agents in diagnostic imaging. MBs have also shown great potential in applications such as molecular imaging, drug delivery, gene therapy and sonothrombolysis. A full understanding of all physical processes underlying the MBs' stability and acoustic behavior is available in the literature. Efforts have been now addressed to the study of chemical and biological features of multifunctional lipid, protein, or polymer shelled MBs. A number of methods of preparation of "smart" MBs for ultrasound image-guided therapy have been recently developed. In this review, different approaches utilized in preparing multifunctional MBs are discussed with specific attention to the current strategies adopted to design MBs with specialized functions. In vitro / in vivo assessment of MBs' stability and activity will be discussed with a particular emphasis on the emerging applications of MBs for the multiple imaging modalities, the effective opening of blood brain barrier, BBB, and for the therapeutic treatment of antimicrobial films.
Publisher: American Chemical Society (ACS)
Date: 10-05-2017
Abstract: Glyconanoparticles that exhibit multivalent binding to lectins are desirable for molecular recognition and therapeutic applications. Herein we explore the use of glycogen nanoparticles as a biosourced glycoscaffold for engineering multivalent glyconanoparticles. Glycogen nanoparticles, a naturally occurring highly branched polymer of glucose, was functionalized with lactose, achieved through copper(I)-catalyzed alkyne-azide cycloaddition chemistry, for targeted interaction with lectins ex situ and on prostate cancer cells. The lactosylated glycogen, which contains terminal β-galactoside moieties, is termed galacto-glycogen (GG), and is found to interact strongly with peanut agglutinin (PNA), a β-galactoside-specific lectin, as observed by optical waveguide lightmode spectroscopy, dynamic light scattering, and quartz crystal microbalance measurements. The GG nanoparticles exhibit multivalent binding to PNA with an affinity constant of 3.4 × 10
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6NR06657G
Abstract: We report polymer capsule-based probes for quantifying the pressure exerted by cells during capsule internalisation (P
Publisher: Elsevier BV
Date: 12-2002
DOI: 10.1016/S0956-053X(02)00084-3
Abstract: Improvement of mechanical properties of recycled mixed plastic waste is one of the fundamental goals in any recycling process. However, polymer immiscibility makes the development of any effective reprocessing method difficult. In this work, a polymer milling process with liquid CO2 was applied to polymeric mixed waste, obtaining a powder material which was successfully utilized as a matrix for a new composite material. Developed materials have interesting mechanical properties and material performance can easily be improved. Investigations on selected mixtures of PP and PE clearly showed evidence of chemical compatibilization.
Publisher: MDPI AG
Date: 18-02-2022
DOI: 10.3390/PHARMACEUTICS14020438
Abstract: Recently, several studies have indicated an increased interest in the scientific community regarding the application of Cannabis sativa plants, and their extracts, for medicinal purposes. This plant of enormous medicinal potential has been legalised in an increasing number of countries globally. Due to the recent changes in therapeutic and recreational legislation, cannabis and cannabinoids are now frequently permitted for use in clinical settings. However, with their highly lipophilic features and very low aqueous solubility, cannabinoids are prone to degradation, specifically in solution, as they are light-, temperature-, and auto-oxidation-sensitive. Thus, plant-derived cannabinoids have been developed for oral, nasal-inhalation, intranasal, mucosal (sublingual and buccal), transcutaneous (transdermal), local (topical), and parenteral deliveries. Among these administrations routes, topical and transdermal products usually have a higher bioavailability rate with a prolonged steady-state plasma concentration. Additionally, these administrations have the potential to eliminate the psychotropic impacts of the drug by its diffusion into a nonreactive, dead stratum corneum. This modality avoids oral administration and, thus, the first-pass metabolism, leading to constant cannabinoid plasma levels. This review article investigates the practicality of delivering therapeutic cannabinoids via skin in accordance with existing literature.
Publisher: Elsevier BV
Date: 11-2021
Publisher: American Chemical Society (ACS)
Date: 29-10-2013
DOI: 10.1021/AM403108Y
Abstract: The mechanical properties of the shell of ultrasonically synthesized lysozyme microbubbles, LSMBs, were evaluated by acoustic interrogation and nanoindentation techniques. The Young's modulus of LSMBs was found to be 1.0 ± 0.3 MPa and 0.6 ± 0.1 MPa when analyzed by flow cytometry and AFM, respectively. The shell elasticity and Young's modulus were not affected by the size of the microbubbles (MBs). The hydrogel-like protein shell of LSMBs offers a softer, more elastic and viscous interface compared to lipid-shelled MBs. We show that the acoustic interrogation technique is a real-time, fast, and high-throughput method to characterize the mechanical characteristics of air-filled microbubbles coated by a variety of materials.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: In this paper, we present some new case ex les where the chemical versatility of poly (vinyl alcohol) (PVA) can be used for potential biomedical applications. PVA, the polymeric material used for designing new nanostructured devices, is water soluble, biocompatible and has excellent physical properties. We point out the possibility of obtaining wall-to-wall chemical hydrogels as well as microgels without diminishing the biocompatibility available in the starting PVA material. Injectability is another important factor to take into account in controlled drug delivery for gene therapy. In this respect, in this paper, established and more innovative methods are prospected in order to obtain particles with dimensions suitable for these applications.
Publisher: American Chemical Society (ACS)
Date: 10-2019
Abstract: The intracellular delivery of functional nanoparticles (NPs) and the release of therapeutic payloads at a target site are central issues for biomedical applications. However, the endosomal entrapment of NPs typically results in the degradation of active cargo, leading to poor therapeutic outcomes. Current advances to promote the endosomal escape of NPs largely involve the use of polycationic polymers and cell-penetrating peptides (CPPs), which both can suffer from potential toxicity and convoluted synthesis/conjugation processes. Herein, we report the use of metal-phenolic networks (MPNs) as versatile and nontoxic coatings to facilitate the escape of NPs from endo/lysosomal compartments. The MPNs, which were engineered from the polyphenol tannic acid and Fe
Start Date: 2021
End Date: 2023
Funder: Australian Research Council
View Funded ActivityStart Date: 2015
End Date: 2019
Funder: Australian Research Council
View Funded ActivityStart Date: 2019
End Date: 2020
Funder: Bill and Melinda Gates Foundation
View Funded ActivityStart Date: 2020
End Date: 2024
Funder: Horizon 2020 Framework Programme
View Funded ActivityStart Date: 2020
End Date: 2020
Funder: Australian Research Council
View Funded ActivityStart Date: 2020
End Date: 2023
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2010
End Date: 2013
Funder: European Commission
View Funded ActivityStart Date: 2015
End Date: 2019
Funder: University of Melbourne
View Funded ActivityStart Date: 2018
End Date: 2018
Funder: Australian Research Council
View Funded ActivityStart Date: 2014
End Date: 2016
Funder: European Commission - FP3
View Funded ActivityStart Date: 2016
End Date: 2020
Funder: European Commission
View Funded ActivityStart Date: 2009
End Date: 2010
Funder: European Commission
View Funded ActivityStart Date: 04-2021
End Date: 04-2024
Amount: $401,955.00
Funder: Australian Research Council
View Funded ActivityStart Date: 06-2015
End Date: 08-2019
Amount: $772,104.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2007
End Date: 04-2008
Amount: $85,530.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2018
End Date: 12-2018
Amount: $639,369.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2018
End Date: 12-2024
Amount: $3,279,502.00
Funder: Australian Research Council
View Funded ActivityStart Date: 06-2020
End Date: 05-2022
Amount: $700,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2021
End Date: 07-2022
Amount: $875,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 10-2022
End Date: 10-2023
Amount: $699,691.00
Funder: Australian Research Council
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