ORCID Profile
0000-0002-4669-0890
Current Organisation
Fondazione IRCCS Istituto Nazionale dei Tumori
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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: Wiley
Date: 02-2006
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: 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: 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: Informa UK Limited
Date: 04-2012
DOI: 10.4161/AUTO.19496
Publisher: Informa UK Limited
Date: 02-01-2016
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.
Location: Norway
No related grants have been discovered for Nadia Zaffaroni.