ORCID Profile
0000-0001-6932-1900
Current Organisations
University of Technology Sydney
,
Shanghai Institute of Ceramics Chinese Academy of Sciences
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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.
Nanomedicine | Biomaterials | Nanotechnology | Nanochemistry and Supramolecular Chemistry
Cancer and Related Disorders | Human Pharmaceutical Treatments (e.g. Antibiotics) | Expanding Knowledge in Technology |
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7PY00385D
Abstract: Enhanced cellular uptake and efficient penetration of nanocarriers inside tumors is paramount to successful anti-cancer therapy.
Publisher: American Chemical Society (ACS)
Date: 05-10-2016
DOI: 10.1021/ACS.MOLPHARMACEUT.6B00410
Abstract: Paclitaxel (PTX)-conjugated micelles provide a promising tool for the treatment of prostate cancer. Core cross-linking by incorporating a disulfide bridge is a useful approach to improving the in vivo stability of polymeric micelles. This paper aims to investigate the effects of different degrees of cross-linking on the antitumor efficacy of micelles formed by poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer. Both two-dimensional (2D) and three-dimensional (3D) in vitro prostate tumor cell models were used to evaluate the un-cross-linked and cross-linked micelles. The cytotoxicity decreased with an increase in the degree of cross-linking upon being tested with 2D cultured cells, and all micelles remained less cytotoxic than free PTX. In the 3D prostate MCTS model, however, there was no statistical difference between the performance of un-cross-linked micelles and free PTX, while increasing cross-linking densities led to significantly relevant decreases in the antitumor efficacy of micelles. These results are contradictory to our previous research using an irreversible cross-linker (1,8-diaminooctane) to stabilize POEGMEA-b-PCEA-PTX conjugate micelles where it was shown that cross-linking accelerates and improves the effects of the micelles when compared to those of un-cross-linked micelles. Further studies that aim to investigate the underlying mechanisms of disulfide bonds when micelles are internalized into cells are desired.
Publisher: Wiley
Date: 20-07-2016
Publisher: Wiley
Date: 22-06-2012
Abstract: Porous collagen scaffolds with micropatterned structures are manufactured using preformed ice micropattern templates. The scaffolds show precisely controlled pore structures and micropattern structures of bioactive substances, which can be tethered by designing a program.
Publisher: Wiley
Date: 07-05-2015
Abstract: A series of thermo-and pH-responsive poly(methyl methacrylate)-block-poly[methacrylic acid-co-di(ethylene glycol) methyl ether methacrylate] PMMA-b-P[MAA-co-DEGMA] block copolymers were synthesized by RAFT polymerization and self-assembled into micelles. The molar ratio of MAA was altered from 0-12% in order to modulate the lower critical solution temperature (LCST) of PDEGMA. The release of the drug albendazole from the micelle was strongly dependent on the temperature and the LCST value of the polymer. Systems below the LCST released the drug slowly while increasing the temperature above the LCST or decreasing the pH value to 5 resulted in the burst-like release of the drug. ABZ delivered in this pH-responsive drug carrier had a higher toxicity than the free drug or the drug delivered in a non-responsive drug carrier.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7TB02902K
Abstract: Albumin-based nanoparticles have been exploited as a useful carrier for the efficient delivery of anti-cancer drugs.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.ACTBIO.2013.12.042
Abstract: Scaffold pore size is an important factor affecting tissue regeneration efficiency. The effect of pore size on cartilage tissue regeneration was compared by using four types of collagen porous scaffolds with different pore sizes. The collagen porous scaffolds were prepared by using pre-prepared ice particulates that had diameters of 150-250, 250-355, 355-425 and 425-500μm. All the scaffolds had spherical large pores with good interconnectivity and high porosity that facilitated cell seeding and spatial cell distribution. Chondrocytes adhered to the walls of the spherical pores and showed a homogeneous distribution throughout the scaffolds. The in vivo implantation results indicated that the pore size did not exhibit any obvious effect on cell proliferation but exhibited different effects on cartilage regeneration. The collagen porous scaffolds prepared with ice particulates 150-250μm in size best promoted the expression and production of type II collagen and aggrecan, increasing the formation and the mechanical properties of the cartilage.
Publisher: American Chemical Society (ACS)
Date: 22-11-2013
DOI: 10.1021/BM4013919
Abstract: Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an hiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of d,l-lactide (3,6-dimethyl-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.
Publisher: SAGE Publications
Date: 05-2011
Abstract: A micropatterned surface with different area ratios of cell-adhesive to nonadhesive surfaces was prepared by micropatterning poly(vinyl alcohol) on a polystyrene plate using photolithography. A gradient pattern of mesenchymal stem cells of different cell densities was generated by culturing the cells on a micropatterned surface. The effects of the cell density gradient on cell functions such as proliferation and differentiation were investigated. Cells seeded at a low density proliferated faster than cells seeded at a high density. Although mesenchymal stem cells seeded at both low and high densities showed osteogenic differentiation, the higher cell seeding density could initiate osteogenic differentiation at a faster rate than the low cell density. And high cell density was required to induce chondrogenic differentiation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4CC00616J
Abstract: A new micelle delivery platform based on albumin coated nanoparticles is able to selectively deliver the payload to cancerous cells while healthy cells remain less affected. The technology is simple and can be used in a one-pot procedure.
Publisher: Wiley
Date: 16-02-2018
Abstract: Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models that can mimic the microenvironment of tissues. MCTS have gained increasing interest in the nano-biotechnology field as they can provide easily accessible information on the performance of nanoparticles without using animal models. Considering that many countries have put restrictions on animals testing, which will only tighten in the future as seen by the recent developments in the Netherlands, 3D models will become an even more valuable tool. Here, an overview on MCTS is provided, focusing on their use in cancer research as most nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter, various types of nanoparticles-from self-assembled block copolymers to inorganic nanoparticles, are discussed. A range of physicochemical parameters including the size, shape, surface chemistry, ligands attachment, stability, and stiffness are found to influence nanoparticles in MCTS. Some of these studies are complemented by animal studies confirming that lessons from MCTS can in part predict the behaviour in vivo. In summary, MCTS are suitable models to gain additional information on nanoparticles. While not being able to replace in vivo studies, they can bridge the gap between traditional 2D in vitro studies and in vivo models.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2BM00096B
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7PY00082K
Abstract: A newly synthesised glucosamine-based monomer was able to undergo controlled polymerisation and retain amine functionality. The resulting polymer had mucoadhesive properties similar to chitosan.
Publisher: SAGE Publications
Date: 02-09-2009
Abstract: The effects of hardystonite (Ca 2 ZnSi 2 O 7 , CSZn) and tricalcium phosphate (β-TCP) on the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) were compared by directly culturing MSCs on ceramic disks (contact mode) or separately culturing cells with ceramic disks (non-contact mode). In non-contact mode, the CSZn ceramic supported MSC proliferation more strongly than did the β-TCP ceramic. However, in contact mode, the MSCs proliferated more quickly on the β-TCP ceramic than they did on the CSZn ceramic. Alkaline phosphatase (ALP) staining and osteogenic gene expression analysis showed that the CSZn and β-TCP ceramics had significant effects on the promotion of the osteogenic differentiation of MSCs in both non-contact and contact mode. Furthermore, in contact mode, the CSZn disk promoted the osteogenic differentiation of MSCs more strongly than did the β-TCP disks. Even without the induction of dexamethasone and β-glycerophosphate, CSZn stimulated the osteogenic differentiation of MSCs. These results suggest that CSZn ceramic would be a useful candidate material for bone regeneration and hard tissue engineering.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5PY01579K
Abstract: The therapeutic potency of platinum-based anticancer drugs can be substantially improved through the use of fructose-coated nanocarrier systems to target cancer cells efficiently.
Publisher: American Vacuum Society
Date: 07-2021
DOI: 10.1116/6.0001012
Abstract: Cellular uptake of nanoparticles plays a crucial role in cell-targeted biomedical applications. Despite abundant studies trying to understand the interaction between nanoparticles and cells, the influence of cell geometry traits such as cell spreading area and cell shape on the uptake of nanoparticles remains unclear. In this study, poly(vinyl alcohol) is micropatterned on polystyrene cell culture plates using ultraviolet photolithography to control the spreading area and shape of in idual cells. The effects of these factors on the cellular uptake of poly(N-(2-hydroxypropyl)methacrylamide)-based micelles were investigated at a single-cell level. Human carcinoma MCF-7 and A549 cells as well as normal Hs-27 and MRC-5 fibroblasts were cultured on micropatterned surfaces. MCF-7 and A549 cells, both with larger sizes, had a higher total micelle uptake. However, the uptake of Hs-27 and MRC-5 cells decreased with increasing spreading area. In terms of cell shapes, MCF-7 and A549 cells with round shapes showed a higher micelle uptake, while those with a square shape had a lower cellular uptake. On the other hand, Hs-27 and MRC-5 cells showed opposite behaviors. The results indicate that the geometry of cells can influence the nanoparticle uptake and may shed light on the design of functional nanoparticles.
Publisher: Wiley
Date: 20-04-2011
DOI: 10.1002/BTPR.592
Abstract: Cell-derived extracellular matrices (ECMs) are a key factor in regulating cell functions in tissue engineering and regenerative medicine. The fact that cells are surrounded by their specific ECM in vivo elicits the need to elucidate the effects of ECM derived from different cell sources on cell functions. Here, three types of ECM were prepared by decellularizing cultured chondrocytes, fibroblasts, and mesenchymal stem cells (MSC) and used for chondrocyte culture to compare their effects on chondrocyte adhesion, proliferation, and differentiation. Chondrocyte adhesion to the chondrocyte-derived ECM was greater than those to the fibroblast- and MSC-derived ECM. Chondrocyte proliferation on the chondrocyte-derived ECM was lower than those on the fibroblast- and MSC-derived ECM. The ECM showed no evident effect on chondrocyte differentiation. The effects of ECM on cell functions depended on the cell source used to prepare the ECM.
Publisher: Elsevier BV
Date: 09-2013
Publisher: American Chemical Society (ACS)
Date: 26-03-2013
DOI: 10.1021/BM400121Q
Abstract: In this study, a novel technique was used for the reversible attachment of folic acid on the surface of polymeric micelles for a tumor-specific drug delivery system. The reversible conjugation is based on the interaction between phenylboronic acid (PBA) and dopamine to form a borate ester. The conjugation is fast and efficient and in vitro experiments via confocal fluorescent microscopy show that the linker is stable in for several hours. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize two various sized water-soluble block copolymer of oligoethylene glycol methylether methacylate and methyl acrylic acid (POEGMEMA(35)-b-PMAA(200) and POEGMEMA(26)-b-PMAA(90)). The platinum drug, oxoplatin, was then subsequently attached to the polymer via ester formation leading to platinum loading of 12 wt % as determined by TGA. The platinum-induced hiphilic block copolymers that consequently led to the formation of micelles of sizes 150 and 20 nm in an aqueous environment with the longer PMAA block forming larger micelles. The small micelles were in addition cross-linked using 1,8-diaminooctane to further stabilize their structure. The targeting ability of folate conjugated polymeric micelles was investigated against two types of tumor cell lines: A549 (-FR) and OVCAR-3 (+FR). The cell line growth inhibitory efficacy of material synthesized was evaluated by using SRB method. The results revealed that folate conjugated micelles showed higher activity in FR + OVCAR-3 cells but not in FR - A549 cells. Similar results were obtained for both small and large micelles without the conjugation of folate. Comparing large and small micelles it can be observed that larger micelles are more efficient, which has been attributed to the lower stability of the smaller micelles. Micelle stabilization via cross-linking could indeed increase the toxicity of the drug carrier.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5PY01360G
Abstract: Poly[(2-(α- d -mannosyloxy)ethyl acrylate)-block-( n -butyl acrylate)], P(ManA- b -BA), and poly[poly(ethylene glycol) methyl ether acrylate]-block-( n -butyl acrylate)], P(OEGMEA- b -BA) diblock copolymers were mixed at various ratios to generate self-assembled structures of different morphologies.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6PY01584K
Abstract: Synthesis of polymeric capsules with good control over the particle size and size distribution is demonstrated via a novel approach involving SPG membrane emulsification.
Publisher: Wiley
Date: 11-10-2023
Abstract: Polymeric micelles are widely used as multifunctional drug carriers of poorly water‐soluble drugs, but the role of drug loading content is often overlooked. The purpose of this study is to investigate the cellular uptake and penetration of polymeric micelles with different drug loading contents and their effects on biological activities. In this study, poly( N ‐(2‐hydroxypropyl) methacrylamide‐co‐methacrylic acid)‐ block ‐poly methyl methacrylate P(HPMA‐co‐MAA)‐ b ‐PMMA micelles are used as a nanocarrier for the encapsulation of the potent anticancer agent ellipticine (EPT). The micelles are loaded with various amounts of EPT and the physicochemical characteristics such as particle size, morphology, and zeta potential of blank and EPT loaded nanoparticles are studied. Moreover, fluorescent lifetime studies confirm that hydrophobic EPT is indeed in the PMMA micelle core. In vitro cytotoxicity tests using the glioma cell line U87MG reveal lower IC 50 values when the cells are incubated with micelle with high drug loading content. The higher toxicity in micelles with higher drug loading content is associated with higher cellular uptake, which is monitored using laser scanning confocal microscopy and flow cytometry. Moreover, higher activity of micelles with higher drug loading is also observed in U87MG multicellular tumor spheroids although the difference is not significant.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7PY01162H
Abstract: Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for ex le, multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed.
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.BBRC.2008.07.112
Abstract: Cartilaginous gene expression decreased when chondrocytes were expanded on cell-culture plates. Understanding the dedifferentiation mechanism may provide valuable insight into cartilage tissue engineering. Here, we demonstrated the relationship between the nuclear shape and gene expression during in vitro expansion culture of chondrocytes. Specifically, the projected nuclear area increased and cartilaginous gene expressions decreased during in vitro expansion culture. When the nuclear deformation was recovered by cytochalasin D treatment, aggrecan expression was up-regulated and type I collagen (Col1a2) expression was down-regulated. These results suggest that nuclear deformation may be one of the mechanisms for chondrocyte dedifferentiation during in vitro expansion culture.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4CC06651K
Abstract: Overexpression of GLUT5 in breast cancer cell lines leads to extensive uptake of fructose bearing nanoparticles.
Publisher: American Chemical Society (ACS)
Date: 27-02-2013
DOI: 10.1021/MZ4000199
Abstract: Nanodiamonds (NDs) are highly promising drug carriers due to their biocompatibility, manipulable surface chemistry, and nonbleaching flourescence. In this communication, we compare the cytotoxicity of three ND-cisplatin systems in which cisplatin was incorporated via direct attachment to the ND surface, physical adsorption within a poly(oligo(ethylene glycol) methyl ether methacrylate) POEGMEMA surface coating, or complexation to 1,1-di-
Publisher: IOP Publishing
Date: 11-07-2011
DOI: 10.1088/1748-6041/6/4/045011
Abstract: Three-dimensional porous scaffolds play an important role in tissue engineering and regenerative medicine. Structurally, these porous scaffolds should have an open and interconnected porous architecture to facilitate a homogeneous cell distribution. Moreover, the scaffolds should be mechanically strong to support new tissue formation. We developed a novel type of funnel-like collagen sponge using embossing ice particulates as a template. The funnel-like collagen sponges could promote the homogeneous cell distribution, ECM production and chondrogenesis. However, the funnel-like collagen sponges deformed during cell culture due to their weak mechanical strength. To solve this problem, we reinforced the funnel-like collagen sponges with a knitted poly(D,L-lactic-co-glycolic acid) (PLGA) mesh by hybridizing these two types of materials. The hybrid scaffolds were used to culture bovine articular chondrocytes. The cell adhesion, distribution, proliferation and chondrogenesis were investigated. The funnel-like structure promoted the even cell distribution and homogeneous ECM production. The PLGA knitted mesh protected the scaffold from deformation during cell culture. Histological and immunohistochemical staining and cartilaginous gene expression analyses revealed the cartilage-like properties of the cell/scaffold constructs after in vivo implantation. The hybrid scaffold, composed of a funnel-like collagen sponge and PLGA mesh, would be a useful tool for cartilage tissue engineering.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB00706C
Abstract: Internalization of rod-like micelles by breast cancer cells is significantly affected by the stiffness of nano-rods.
Publisher: SAGE Publications
Date: 08-2013
Abstract: Appropriate pore structures and mechanical properties are required for scaffolds that are used for tissue engineering and regenerative medicine. In this study, pre-prepared ice particulates were used as a porogen material to prepare collagen porous scaffolds with well-controlled pore structures and improved mechanical properties. Porogen ice particulates initiated the formation of interconnected large spherical pores surrounded by small pores. The large spherical pores were well compacted and increased the elastic modulus of the scaffolds. The unique pore structures facilitated cell penetration, resulting in a homogeneous cell distribution throughout the scaffolds. The excellent mechanical properties protected the scaffolds from deformation during cell culturing and implantation. The collagen porous scaffolds facilitated cartilage regeneration when bovine articular chondrocytes were cultured in these scaffolds. The use of pre-prepared ice particulates as a porogen material proved to be a useful method to control the pore structure and improve the mechanical properties of collagen-based porous scaffolds.
Publisher: American Chemical Society (ACS)
Date: 16-10-2014
DOI: 10.1021/BM501205X
Abstract: Novel biocompatible polyion complex micelles, containing bovine serum albumin (BSA), polymer, and oligonucleotide, were synthesized as a generation of vectors for the gene transfection. Maleimide-terminated poly((N,N-dimethyl amino) ethyl methacrylate) (PDMAEMA) was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently deprotected. Precise one to one albumin-PDMAEMA bioconjugates have been achieved via 1,4-addition with the free thiol group on Cys34 on the BSA protein. SDS-PAGE and GPC (water) confirmed and quantified the successful conjugation. The conjugation efficiency was found to be independent of the molecular weight of PDMAEMA. After careful pH adjustment, the conjugate could efficiently condense anticancer oligonucleotide, ISIS 5132, which resulted in particles of 15-35 nm with a negative zeta-potential. The size was easily controlled by the polymer chain length. The albumin corona provides complete protection of the cationic polymer and genetic drug, which gave rise to lower potential toxicity from the polymer and higher gene transfection efficiency. Although a control experiment with a traditional PEG-based polyion complex micelle could deliver the drug just as effectively, if not more so, to the ovarian cancer cell line OVCAR-3, this carrier had no selectivity toward cancerous cells and proved just as toxic to HS27 (fibroblast) cell line. In contrast, the albumin-coated particles demonstrated desirable selectivity toward cancerous cells and have been shown to have outstanding performance in the cytotoxicity tests of several carcinoma monolayer cell models. In addition, the complex micelles were able to destroy pancreatic multicellular tumor spheroids, while free ISIS 5132 could not penetrate the spheroid at all. Hence, albumin-coated/oligonucleotide complex micelles are far more promising than the most classical gene delivery vectors.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB01613E
Abstract: Nanoparticles based on albumin have made an impact in the treatment of various cancers. However, these nanoparticles are not suitable for the delivery of nucleic acid-based drugs. Here, we have evaluated the safety of polymer–albumin conjugates as a carrier for charged drugs such as oligonucleotides.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6PY01188H
Abstract: Prodrug (gemcitabine)-based polymer coated nanodiamonds as stimuli-responsive drug delivery platforms for the treatment of pancreatic cancer.
Publisher: American Chemical Society (ACS)
Date: 13-04-2017
Abstract: Natural variations in pH levels of tissues in the body make it an attractive stimuli to trigger drug release from a delivery vehicle. A number of such carriers have been developed but achieving high drug loading combined with low leakage at physiological pH and tunable controlled release at the site of action is an ongoing challenge. Here we report a novel strategy for the synthesis of entirely hydrophilic stimuli-responsive nanocarriers with high passive loading efficiency of doxorubicin (DOX), which show good stability at pH 7 and rapid tunable drug release at intracellular pH. The particles (D
Publisher: American Chemical Society (ACS)
Date: 14-12-2019
DOI: 10.1021/ACS.BIOMAC.8B01406
Abstract: Glycopolymer-coated nanoparticles have attracted significant interest over the past few years, because of their selective interaction with carbohydrate receptors found on the surface of cells. While the type of carbohydrate determines the strength of the ligand-receptor interaction, the presentation of the sugar can be highly influential as the carbohydrate needs to be accessible in order to display good binding. To shine more light on the relationship between nanoparticle structure and cell uptake, we have designed several micelles based on fructose containing block copolymers, which are selective to GLUT5 receptors found on breast cancer cell lines. The polymers were based on poly-d,l-lactide (PLA), poly(2-hydroxyethyl) acrylate (PHEA), and poly(1- O-acryloyl-β-d-fructopyranose) (P[1- O-AFru]). A set of six micelles was synthesized based on four fructose containing micelles (PLA
Publisher: American Chemical Society (ACS)
Date: 21-06-2016
Abstract: While the shape effect of nanoparticles on cellular uptake has been frequently studied, no consistent conclusions are available currently. The controversy mainly focuses on the cellular uptake of elongated (i.e., filaments or rod-like micelles) as compared to spherical (i.e., micelles and vesicles) nanoparticles. So far, there is no clear trend that proposes the superiority of spherical or nonspherical nanoparticles with conflicting reports available in the literature. One of the reasons is that these few reports available deal with nanoparticles of different shapes, surface chemistries, stabilities, and aspects ratios. Here, we investigated the effect of the aspect ratio of cylindrical micelles on the cellular uptake by breast cancer cell lines MCF-7 and MDA-MB-231. Cylindrical micelles, also coined rod-like micelles, of various length were prepared using fructose-based block copolymers poly(1-O-methacryloyl-β-d-fructopyranose)-b-poly(methyl methacrylate). The critical water content, temperature, and stirring rate that trigger the morphological transition from spheres to rods of various aspect ratios were identified, allowing the generation of different kinetically trapping morphologies. High shear force as they are found with high stirring rates was observed to inhibit the formation of long rods. Rod-like micelles with length of 500-2000 nm were subsequently investigated toward their ability to translocate in breast cancer cells and penetrate into MCF-7 multicellular spheroid models. It was found that shorter rods were taken up at a higher rate than longer rods.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9LC00872A
Abstract: Gradient-sized spheroids can be simultaneously generated on a single chip using a liquid-dome method assisted by the surface tension. The facile method can be used for investigation of the size-dependent behaviors of spheroids in biomedical research.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.BIOMATERIALS.2010.12.016
Abstract: Development of autologous scaffolds has been highly desired for implantation without eliciting adverse inflammatory and immune responses. However, it has been difficult to obtain autologous scaffolds by tissue decellularization because of the restricted availability of autologous donor tissues from a patient. Here we report a method to prepare autologous extracellular matrix (aECM) scaffolds by combining culture of autologous cells in a three-dimensional template, decellularization, and template removal. The aECM scaffolds showed excellent biocompatibility when implanted. We anticipate that "Full Autologous Tissue Engineering" can be realized to minimize undesirable host tissue responses by culturing the patient's own cells in an aECM scaffold.
Publisher: Wiley
Date: 21-08-2014
Abstract: We show for the first time how polymeric nanotubes (NTs) based on self-assembled conjugates of polymers and cyclic peptides can be used as an efficient drug carrier. RAPTA-C, a ruthenium-based anticancer drug, was conjugated to a statistical co-polymer based on poly(2-hydroxyethyl acrylate) (pHEA) and poly(2-chloroethyl methacrylate) (pCEMA), which formed the shell of the NTs. Self-assembly into nanotubes (length 200-500 nm) led to structures exhibiting high activity against cancer cells.
Publisher: American Chemical Society (ACS)
Date: 12-04-2011
DOI: 10.1021/LA200487W
Abstract: Micropatterned surfaces are very useful to control cell microenvironment and investigate the physical effects on cell function. In this study, poly(vinyl alcohol) (PVA) micropatterns on polystyrene cell-culture plates were prepared using UV photolithography. Cell adhesive polystyrene geometries of triangle, square, pentagon, hexagon, and circle were surrounded by cell nonadhesive PVA to manipulate cell shapes. These different geometries had the same small surface areas for cell spreading. Human mesenchymal stem cells (MSCs) were cultured on the micropatterned surface, and the effect of cell geometry on adipogenic differentiation was investigated. MSCs adhered to the geometric micropatterns and formed arrays of single cell with different shapes. The distribution patterns of actin filaments were similar among these cell shapes and remolded during adipogenesis. The adipogenic differentiation potential of MSCs was similar on the small size triangular, square, pentagonal, hexagonal, and circular geometries according to lipid vacuoles staining. This simple micropatterning technique using photoreactive molecules will be useful for creating micropatterns of arbitrary design on an organic surface, and cell functions can be directly and systematically compared on a single surface without external factors resulting from separate cell culture and coating method.
Publisher: Elsevier BV
Date: 08-2015
Publisher: IOP Publishing
Date: 25-10-2021
Abstract: Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal organoid culture. Here, we present a method to model the peristalsis for human colon tumor organoids on a microfluidic chip. The chip contains hundreds of lateral microwells and a surrounding pressure channel. Human colon tumor organoids growing in the microwell were cyclically contracted by pressure channel, mimicking the in vivo mechano-stimulus by intestinal muscles. The chip allows the control of peristalsis litude and rhythm and the high throughput culture of organoids simultaneously. By applying 8% litude with 8 ∼ 10 times min −1 , we observed the enhanced expression of Lgr5 and Ki67. Moreover, ellipticine-loaded polymeric micelles showed reduced uptake in the organoids under peristalsis and resulted in compromised anti-tumor efficacy. The results indicate the importance of mechanical stimuli mimicking the physiological environment when using in vitro models to evaluate nanoparticles. This work provides a method for attaining more reliable and representative organoids models in nanomedicine.
Publisher: American Chemical Society (ACS)
Date: 10-01-2019
Publisher: Wiley
Date: 24-02-2017
Abstract: The ruthenium complex-dichlororuthenium (II) (p-cymene) (1,3,5-triaza-7-phosphaadamantane) (RAPTA-C)-has shown to be remarkably effective at suppressing the growth of solid tumor metastases. However, poor delivery efficacy and the lack of targeting ability of the common drug delivery system pose significant obstacles to maximize the therapeutic benefit of RAPTA-C. Inspired by the overexpression of GLUT5 transporter on the surface of breast cancer tissues but not the healthy mammary tissues, the use of d-fructose as the targeting moiety of the drug carrier can significantly improve the cellular uptake of nanoparticles, thus further enhancing the therapeutic efficiency of RAPTA-C. In this work, fructose-micelles and 2-hydroxyethyl acrylate (HEA)-micelles are prepared to investigate the difference in cellular uptake. It is found that glycopolymer leads to an increased uptake by breast cancer cells, while the HEA-micelles show less uptake. This behavior is also reflected by the slightly faster movement of fructose-coated micelles in MCF-7 tumor spheroid models using light sheet microscopy as analytical tool. The incorporation of RAPTA-C into micelles can enhance the inhibitory effect of the ruthenium drug demonstrated using invasion, chemotaxis, and haptotaxis assays. As a result, fructose-coated nanoparticles can be a promising drug delivery platform of RAPTA-C for the treatment of metastatic breast cancer.
Publisher: American Chemical Society (ACS)
Date: 23-01-2018
DOI: 10.1021/ACS.BIOMAC.7B01592
Abstract: The introduction of a strategy toward polymer/nanodiamond hybrids with high polymer grafting density and accessible polymer structural characterization is of critical importance for nanodiamonds' surface modification and bioagent attachment for their biomedical application. Here, we report a glycopolymer/nanodiamond hybrid drug delivery system, which was prepared by grafting amonafide-conjugated glycopolymers onto the surface of nanodiamonds via oxime ligation. Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose)-b-poly(3-vinylbenzaldehyde-co-methyl methacrylate), featuring pendant aldehyde groups, is prepared via RAFT polymerization. The anticancer drug amonafide is conjugated to the polymer chains via imine chemistry, resulting in acid-degradable imine linkages. The obtained amonafide-conjugated glycopolymers are subsequently grafted onto the surface of aminooxy-functionalized nanodiamonds via oxime ligation. The molecular weight of the conjugated polymers is characterized by size-exclusion chromatography (SEC), while the successful conjugation and corresponding grafting density is assessed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric aanalysis (TGA). Our results indicate that the mass percentage of amonafide in the polymer chains is around 17% and the surface density of polymer chains is 0.24 molecules/nm
Publisher: Informa UK Limited
Date: 2009
Publisher: Wiley
Date: 24-05-2012
DOI: 10.1002/JBM.A.34150
Abstract: Extracellular matrix (ECM) scaffolds derived from cultured cells have drawn increasing attention for use in tissue engineering. We have developed a method to prepare cultured cell-derived ECM scaffolds by combining three-dimensional cell culture, decellularization, and selective template removal. Cell-ECM-template complexes were first formed by culture of cells in a poly(lactic-co-glycolic acid) (PLGA) mesh template to deposit their own ECM. The complexes were subsequently decellularized to remove cellular components. Finally, the PLGA template was selectively removed to obtain the ECM scaffolds. Seven decellularization methods were compared for their decellularization effects during scaffold preparation. They were: freeze-thaw cycling (-80°C, six times) with ammonia water (25 mM) 0.1% Triton™ X-100 (TX100) with 1.5M KCl aqueous solution freeze-thaw cycling alone ammonia water alone TX100 extraction osmotic shock with 1.5M KCl and freeze-thaw cycling with 3M NaCl. Among these methods, the methods of freeze-thaw cycling with NH(4) OH and TX100 with 1.5M KCl showed the best effect on the removal of cellular components from the complexes, while the other five methods could only partially remove cellular components. The ECM scaffolds prepared by these two methods had similar gross appearances and microstructures. In vivo implantation of the ECM scaffolds prepared by these two methods induced mild host responses. The two decellularization methods were demonstrated to be effective for preparation of cultured cell-derived ECM scaffolds.
Publisher: Wiley
Date: 04-11-2016
Abstract: Carboxyl end-functionalized poly[poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)] and its block copolymer with gemcitabine substituted poly(N-hydroxysuccinimide methacrylate) [PGem-block-P(PEGMEMA)] are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. Then, two polymers are grafted onto the surface of amine-functionalized nanodiamonds to obtain [P(PEGMEMA)]-grafted nanodiamonds (ND-PEG) and [PGem-block-P(PEGMEMA)]-grafted nanodiamonds (ND-PF). Gemcitabine is physically absorbed to ND-PEG to produce ND-PEG (Gem). Two polymer-grafted nanodiamonds (i.e., with physically absorbed gemcitabine ND-PEG (Gem) and with chemically conjugated gemcitabine ND-PF) are characterized using attenuated total reflectance infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis. The drug release, cytotoxicity (to seed human pancreatic carcinoma AsPC-1 cells), and cellular uptake of ND-PEG (Gem) and ND-PF are also investigated.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.ACTBIO.2015.12.020
Abstract: Macromolecular ruthenium (Ru) complexes are a promising avenue to better, and more selective, chemotherapeutics to treat metastatic cancers. In our previous research, hiphilic block copolymeric micelles carrying RAPTA-C (RuCl2(p-cymene)(PTA)) were demonstrated to improve the cellular uptake and cytotoxicity of RAPTA-C (Blunden et al., 2013). However, the anti-metastatic effect of RAPTA-C conjugated polymeric micelles is yet to be established. In this work, we investigated the anti-metastatic effects of RAPTA-C conjugated micelles in both 2D and 3D in vitro breast tumor cell models in comparison with free RAPTA-C. RAPTA-C conjugated micelles showed an improved anti-metastatic effect compared with RAPTA-C for 2D cultured breast tumor cells. RAPTA-C micelles selectively targeted the metastatic tumor cells over the nontumorigenic CHO cells. 3D MCTS assays showed that RAPTA-C conjugated micelles showed a cell growth inhibition similar to that of ten times of the free drug. Further improvement of the RAPTA-C delivery vehicle may provide useful tools to harness ruthenium compounds for metastatic cancer therapy. The interest in ruthenium drugs stem from their anti-metastatic effect. In contrast to other metal-based drugs that inhibit the growth of tumor cells, ruthenium drugs seem less toxic, but have a pronounce effect on the migration of cancer cells. The ruthenium drug chosen here, RAPTA-C, is capable of inhibiting migration as shown in various assays here. In this publication, we could show for the first time that this effect is enhanced when the drug is delivered using micelles. Important in particular is that the effect is more pronounced in cancerous breast cancer cells while RAPTA-C delivered in micelles does not seem to show any effect on healthy cells. We believe that the presented micelles are suitable carriers for this anti-metastatic drug. The design of the micelle would also allow the encapsulation of other drugs in future studies creating a potentially powerful bullet.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.ACTBIO.2011.09.008
Abstract: The capacity to induce rapid vascular ingrowth during new bone formation is an important feature of biomaterials that are to be used for bone regeneration. Akermanite, a Ca-, Mg- and Si-containing bioceramic, has been demonstrated to be osteoinductive and to promote bone repair. This study further demonstrates the ability of akermanite to promote angiogenesis and investigates the mechanism of this behavior. The akermanite ion extract predominantly caused Si-ion-stimulated proliferation of human aortic endothelial cells. The Si ion in the extract was the most important component for the effect and the most effective concentration was found to be 0.6-2 μg ml(-1). In this range of Si ion concentration, the stimulating effect of the ceramic ion extract was demonstrated by the morphology of cells at the primary, interim and late stages during in vitro angiogenesis using ECMatrix™. The akermanite ion extract up-regulated the expression of genes encoding the receptors of proangiogenic cytokines and also increased the expression level of genes encoding the proangiogenic downstream cytokines, such as nitric oxide synthase and nitric oxide synthesis. Akermanite implanted in rabbit femoral condyle model promoted neovascularization after 8 and 16 weeks of implantation, which further confirmed its stimulation effect on angiogenesis in vivo. These results indicate that akermanite ceramic, an appropriate Si ion concentration source, could induce angiogenesis through increasing gene expression of proangiogenic cytokine receptors and up-regulated downstream signaling. To our knowledge, akermanite ceramic is the first Si-containing ceramic demonstrated to be capable of inducing angiogenesis during bone regeneration.
Publisher: Wiley
Date: 14-01-2020
Abstract: Cancer spheroids have structural, functional, and physiological similarities to the tumor, and have become a low-cost in vitro model to study the physiological responses of single cells and therapeutic efficacy of drugs. However, the tiny spheroid, made of a cluster of high-density cells, is highly scattering and absorptive, which prevents light microscopy techniques to reach the depth inside spheroids with high resolution. Here, a method is reported for super-resolution mapping of single nanoparticles inside a spheroid. It first takes advantage of the self-healing property of a "nondiffractive" doughnut-shaped Bessel beam from a 980 nm diode laser as the excitation, and further employs the nonlinear response of the 800 nm emission from upconversion nanoparticles, so that both excitation and emission at the near-infrared can experience minimal loss through the spheroid. These strategies lead to the development of a new nanoscopy modality with a resolution of 37 nm, 1/26th of the excitation wavelength. This method enables mapping of single nanoparticles located 55 µm inside a spheroid, with a resolution of 98 nm. It suggests a solution to track single nanoparticles and monitor their release of drugs in 3D multicellar environments.
Publisher: American Chemical Society (ACS)
Date: 07-02-2018
DOI: 10.1021/ACS.BIOCONJCHEM.8B00032
Abstract: PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anticancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition-fragmentation chain transfer) polymerization with poly(ethylene glycol methyl ether methacrylate) as comonomer and poly(methyl methacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt % of PENAO MA. The different block copolymers self-assembled into micelle structures, varying in size and stability (D
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3CC49100E
Abstract: Boronic esters between 1,2-benzodiols and boronic acids are an efficient way for bioconjugation. The ester is stable at physiological condition, but it cleaves very slowly at acidic pH values found in the endosomes and lysosomes. During apoptosis, the boronic ester is cleaved, most likely due to the influx of Ca 2+ ions and the oxidation of 1,2-benzodiols.
Publisher: American Chemical Society (ACS)
Date: 04-10-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC04986F
Abstract: Light sheet microscopy reveals the low stability of polyelectrolyte–protein complexes in spheroids.
Publisher: Informa UK Limited
Date: 08-05-2012
Publisher: Informa Healthcare
Date: 09-11-2010
DOI: 10.1517/14712598.2010.534079
Abstract: Biomimetic scaffolds and substrates of extracellular matrices (ECMs) play an important role in the regulation of cell function and in the guidance of new tissue regeneration, as an ECM has the intrinsic cues necessary to communicate with and dictate to cells. This paper reviews the latest developments in ECM scaffolds and substrates obtained from decellularized tissues, organs or cultured cells and their application in tissue engineering. The ECM composition, structure, interaction with surrounding cells, preparation method and usage in the regeneration of various tissues and organs are summarised. The advantages and challenges of decellularized matrices are highlighted. Similarity in the composition, microstructure and biomechanical properties of the decellularized scaffolds and substrates to those of the native tissues and organs maximizes the promotion effect in the regeneration of both structural and functional tissues and organs. Simple tissues as well as complicated organs have been decellularized and decellularization methods have been optimized to completely remove the cellular components while keeping the ECM intact.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.BIOMATERIALS.2012.05.038
Abstract: The introduction of bioactive molecules into three-dimensional porous scaffolds to mimic the in vivo microenvironment is a promising strategy for tissue engineering and stem cell research. In this study, bone morphogenetic protein-4 (BMP4) was spatially immobilized in a collagen-PLGA hybrid scaffold with a fusion BMP4 composed of an additional collagen-binding domain derived from fibronectin (CBD-BMP4). CBD-BMP4 bound to the collagen-PLGA hybrid scaffold and the BMP4-immobilized hybrid scaffold supported cell adhesion and proliferation. The osteogenic induction effect of the immobilized CBD-BMP4 was investigated with three-dimensional culture of human bone marrow-derived mesenchymal stem cells in the BMP4-immobilized collagen-PLGA hybrid scaffold. The in vivo implantation experiment demonstrated that the immobilized CBD-BMP4 maintained its osteoinductive activity, being capable of up-regulating osteogenic gene expression and biomineralization. The strong osteoinductivity of the BMP4-immobilized scaffold suggests it should be useful for bone tissue engineering, stem cell function manipulation and bone substitutes.
Publisher: American Chemical Society (ACS)
Date: 23-01-2015
DOI: 10.1021/MA502263X
Publisher: American Chemical Society (ACS)
Date: 17-04-2015
DOI: 10.1021/ACS.BIOMAC.5B00282
Abstract: The 2D monolayer cell culture model is often the first step in the prediction of the success or failure of a nanoparticle-based drug delivery system. However, there is often poor translation between the 2D monolayer in vitro results and the nanoparticle-drug performance in vivo. One possible way of bridging this gap is the use of multicellular tumor spheroids (MCTSs) as an intermediate in vitro model due to its 3D structure. This paper aims to quantify and compare the results obtained from traditional 2D monolayer cell cultures and 3D MCTS by studying the cytotoxic effects of free paclitaxel (PTX) and paclitaxel, which has been conjugated to a poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer and self-assembled to give a micellar delivery system. The core of the micelle was cross-linked with a diamino nondegradable cross-linker to compare the effects of micelle stability on the results. Although the 2D prostate tumor cell culture results indicated that all micellar variants (IC50: 193-271 nM) were significantly less toxic than free paclitaxel (IC50: 15.2 nM), the micelles showed faster and higher cytotoxicity than free PTX in the 3D prostate MCTS. The cross-linking of micelles even showed accelerated antitumor activities to the MCTS compared with un-cross-linked micelles. The results indicate that DAO-cross-linked POEGMEA-b-PCEA-PTX conjugate micelles will be a useful nanodrug carrier for prostate cancer therapy. MCTS offers a very promising method of incorporating 3D structures into in vitro testing.
Publisher: Wiley
Date: 04-12-2020
Abstract: It is known that the size of gold nanoparticles (GNPs) is not the only determining factor in the uptake by cells such as cancer cells. The surface functionalization plays a crucial role, in particular the nature of the ligand as well as the molecular weight and the grafting density. Here, poly(2-hydroxy ethyl) acrylate (pHEA) with molecular weights ranging from 10, 20 to 39 g mol
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4BM00323C
Abstract: The penetration of HPMA-based micelles into multicellular tumor spheroids depends on transcellular transport from peripheral to inner cells. Stabilisation by crosslinking facilitated the penetration.
Publisher: American Chemical Society (ACS)
Date: 17-03-2017
DOI: 10.1021/ACS.BIOCONJCHEM.6B00698
Abstract: Albumin-based nanoparticles are widely used to delivery anticancer drug because they promote the accumulation of drugs in tumor sites. Nanoparticles with surface immobilized albumin are widely described in literature, although mixed nanoparticles with systematically modified ratios between albumin and PEG-based material are less common. In this work, hybrid nanoparticles were prepared by coassembly of a PEG-based hiphilic block copolymer together with a polymer-protein conjugate. Poly(oligo(ethylene glycol) methyl ether acrylate)-poly(ε-caprolactone) (POEGMEA-PCL) was prepared by a combination of ring-opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, while the polymer-protein conjugate was obtained by reacting poly(ε-caprolactone) with bovine serum albumin (BSA-PCL). Co-assembly of both hiphiles at different ratios, with and without curcumin as a drug, led to hybrid nanoparticles with various amount of albumin on the particle surface. The resulting hybrid nanoparticles were similar in size (100-120 nm), but increasing the amount of albumin on the surface led to a more-negative ζ potential. The cytotoxicity of the curcumin-loaded nanoparticles was examined on several cell lines. The curcumin-loaded nanoparticles with high amount of albumin led to high cytotoxicity against breast cancer cell lines (MDA-MB-231 and MCF-7), which coincided with high cellular uptake. However, the cytotoxicity of the curcumin-loaded nanoparticles against CHO cells and RAW264.7 cells was reduced, suggesting that albumin can facilitate selectivity toward cancer cells.
Publisher: SAGE Publications
Date: 09-02-2012
Abstract: Angiogenesis is an important process used to guide the regeneration of functional tissues and organs. The incorporation of inductive cues into scaffolds to control angiogenesis is an attractive strategy for scaffold preparation. Four mesh-type scaffolds, including a vascular endothelial growth factor-embedded poly(d,l-lactic- co-glycolic acid) mesh, a vascular endothelial growth factor-coated poly(d,l-lactic- co-glycolic acid) mesh, a collagen-coated poly(d,l-lactic- co-glycolic acid) mesh, and a poly(d,l-lactic- co-glycolic acid) mesh, were compared for their inductive effects on the formation of a micropatterned capillary network. Following subcutaneous implantation, all of the scaffolds induced the formation of micropatterned capillary networks, as observed at 2 and 6 weeks after implantation. The vascular endothelial growth factor-embedded mesh and the vascular endothelial growth factor-coated mesh promoted a higher degree of blood vessel formation than the collagen-coated mesh and the poly(d,l-lactic- co-glycolic acid) mesh. The capillary density in the vascular endothelial growth factor-embedded mesh and the vascular endothelial growth factor-coated mesh increased with time following implantation. The macrophages that surrounded the scaffolds were similar for all the meshes. The microstructure of the poly(d,l-lactic- co-glycolic acid) mesh determined the micropattern of the capillary network, and vascular endothelial growth factor provided a synergistic effect on the micropatterned angiogenesis process.
Publisher: Wiley
Date: 22-02-2023
Abstract: Multicellular spheroids and organoids are promising in vitro 3D models in personalized medicine and drug screening. They replicate the structural and functional characteristics of human organs in vivo. Microfluidic technology and micro‐nano fabrication can fulfill the high requirement of the engineering approach in the growing research interest in spheroids and organoids. In this review, spheroids and organoids are comparatively introduced. Then it is illustrated how spheroids‐ and organoids‐on‐a‐chip technology facilitates their establishment, expansion, and application through spatial‐temporal control, mechanical cues modeling, high‐throughput analysis, co‐culture, multi‐tissue interactions, biosensing, and bioimaging integration. The potential opportunities and challenges in developing spheroids‐ and organoids‐on‐a‐chip technology are finally outlooked.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.BBRC.2009.01.174
Abstract: The effect of cell density on the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) was investigated by using a patterning technique to induce the formation of a cell density gradient on a micropatterned surface. The adipogenic differentiation of MSCs at a density gradient from 5 x 10(3) to 3 x 10(4) cells/cm2 was examined. Lipid vacuoles were observed at all cell densities after 1-3 weeks of culture in adipogenic differentiation medium although the lipid vacuoles were scarce at the low cell density and abundant at the high cell density. Real-time RT-PCR analysis showed that adipogenesis marker genes encoding peroxisome proliferator-activated receptor gamma2 (PPARgamma2), lipoprotein lipase (LPL), and fatty acid binding protein-4 (FABP4) were detected in the MSCs cultured at all cell densities. The results suggest that there was no apparent effect of cell density on the adipogenic differentiation of human MSCs.
Publisher: Wiley
Date: 30-12-2011
DOI: 10.1002/JBM.A.34003
Abstract: The loss of cartilaginous phenotype during in vitro expansion culture of chondrocytes is a major barrier for the application of cartilage tissue engineering. The use of matrices mimicking the in vivo extracellular matrix (ECM) microenvironment is anticipated to be an efficient method to suppress chondrocyte phenotype loss. In this study, we developed several types of ECM derived from serially passaged chondrocytes for use as cell-culture substrata and compared their effects on chondrocyte functions. Primary bovine chondrocytes and serially passaged chondrocytes (at passages 2 and 6) were cultured on tissue-culture polystyrene. After culture, the cellular components were selectively removed from the ECM deposited by the cells. The remaining ECM proteins were used as cell-culture substrata. The composition of the deposited ECM depended on the culture stage of the serially passaged chondrocytes used for the ECM production. The deposited ECM supported the adhesion and proliferation of chondrocytes. The effects of the ECM on the chondrocyte dedifferentiation during in vitro passage culture differed dramatically depending on the phenotype of the chondrocytes used to produce the ECM. The primary chondrocyte-derived ECM delayed the chondrocyte dedifferentiation during in vitro passage culture and is a good candidate for chondrocyte subculture for tissue engineering.
Publisher: Informa UK Limited
Date: 12-2012
Publisher: American Chemical Society (ACS)
Date: 09-02-2016
DOI: 10.1021/ACS.BIOMAC.5B01537
Abstract: An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an ex le of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12 Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7CC09619D
Abstract: A λ-orthogonal reaction system is introduced, where visible light induced radical thiol–ene and UV light induced NITEC (Nitrile-Imine mediated Tetrazole–Ene Conjugation) ligations are consecutively employed to fabricate and functionalize PEG-based hydrogels.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2SM25718A
Publisher: American Chemical Society (ACS)
Date: 14-11-2016
DOI: 10.1021/ACS.BIOMAC.6B01653
Abstract: Although micelles are commonly used for drug delivery purposes, their long-term fate is often unknown due to photobleaching of the fluorescent labels or the use of toxic materials. Here, we present a metal-free, nontoxic, nonbleaching, fluorescent micelle that can address these shortcomings. A simple, yet versatile, profluorescent micellar system, built from hiphilic poly(p-phenylenevinylene) (PPV) block copolymers, for use in drug delivery applications is introduced. Polymer micelles made from PPV show excellent stability for up to 1 year and are successfully loaded with anticancer drugs (curcumin or doxorubicin) without requiring introduction of physical or chemical cross-links. The micelles are taken up efficiently by the cells, which triggers disassembly, releasing the encapsulated material. Disassembly of the micelles and drug release is conveniently monitored as fluorescence of the single polymer chains appear, which enables not only to monitor the release of the payload, but in principle also the fate of the polymer over longer periods of time.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5PY00661A
Abstract: Curcumin can act as a multicolor photoinitiator in free radical photopolymerization under air upon exposure to household LED bulbs.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.BIOMATERIALS.2010.04.019
Abstract: Three-dimensional porous scaffolds of collagen have been widely used for tissue engineering and regenerative medicine. In this study, we fabricated funnel-like collagen sponges with open surface pore structures by a freeze-drying method that used embossing ice particulates as a template. By controlling the size of the ice particulates and the temperature of freezing, collagen sponges with different pore structures were prepared. To investigate the effects of different pore structures on cartilage regeneration, the funnel-like collagen sponges were used to culture bovine articular chondrocytes. Scaffolds that were prepared with 400microm ice particulate templates and a freezing temperature of -3 degrees C resulted in the best cell distribution, ECM production, and chondrogenesis. Although funnel-like collagen sponges prepared with 400microm ice particulate templates and a freezing temperature of -1 degrees C and 720microm ice particulates and a freezing temperature of -3 degrees C, showed even cell distribution, the cell seeding efficiencies and sGAG amount per cell were low. However, the scaffolds prepared with 400microm ice particulate templates and a freezing temperature of -5 degrees C or -10 degrees C showed a limited effect on the improvement of cell distribution and chondrogenesis. Control collagen sponges without ice particulates failed to support the formation of homogenous cartilage-like tissue. These results indicate that funnel-like collagen sponges were superior to control collagen sponges and that scaffolds prepared with 400microm ice particulate templates at -3 degrees C were optimal for cartilage tissue engineering.
Publisher: Wiley
Date: 08-09-2021
Abstract: Mammary tumor organoids have become a promising in vitro model for drug screening and personalized medicine. However, the dependency on the basement membrane extract (BME) as the growth matrices limits their comprehensive application. In this work, mouse mammary tumor organoids are established by encapsulating tumor pieces in non‐adhesive alginate. High‐throughput generation of organoids in alginate microbeads is achieved utilizing microfluidic droplet technology. Tumor pieces within the alginate microbeads developed both luminal‐ and solid‐like structures and displayed a high similarity to the original fresh tumor in cellular phenotypes and lineages. The mechanical forces of the luminal organoids in the alginate capsules are analyzed with the theory of the thick‐wall pressure vessel (TWPV) model. The luminal pressure of the organoids increase with the lumen growth and can reach 2 kPa after two weeks’ culture. Finally, the mammary tumor organoids are treated with doxorubicin and latrunculin A to evaluate their application as a drug screening platform. It is found that the drug response is related to the luminal size and pressures of organoids. This high‐throughput culture for mammary tumor organoids may present a promising tool for preclinical drug target validation and personalized medicine.
Publisher: Mary Ann Liebert Inc
Date: 06-2010
Publisher: American Chemical Society (ACS)
Date: 03-08-2016
DOI: 10.1021/ACS.BIOMAC.6B00754
Abstract: Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 μg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5TB02576A
Abstract: Using proteins as the hydrophilic moiety can dramatically improve the biodegradability and biocompatibility of self-assembled hiphilic nanoparticles in the field of nanomedicine.
Publisher: Wiley
Date: 16-02-2012
DOI: 10.1002/BTPR.1520
Abstract: Micropatterning of biological cues is important for the guided formation of neuronal outgrowth and neuronal differentiation. Nerve growth factor (NGF) was micropatterned in a three-dimensional collagen sponges by using micropatterned ice lines that were composed of collagen and NGF. The micropatterned ice lines were prepared by a dispersing machine. PC12 cells were cultured in the NGF-micropatterned collagen sponges and showed micropatterned neurite outgrowth. The neurite outgrowth followed the micropattern of NGF with more neurite outgrowth in the collagen/NGF lines than in the regions between the collagen/NGF lines. The micropattern of the NGF and the neurite network of the PC12 cells can be manipulated by controlling the micropattern of the NGF. The three-dimensional porous scaffolds prepared by this method will have a potential application for the regeneration and repair of the nervous system.
Publisher: Oxford University Press (OUP)
Date: 12-2009
Publisher: American Chemical Society (ACS)
Date: 24-06-2015
DOI: 10.1021/ACS.BIOMAC.5B00299
Abstract: Inspired by upregulated levels of fucosylated proteins on the surfaces of multiple types of cancer cells, micelles carrying β-l-fucose and β-d-glucose were prepared. A range of block copolymers were synthesized by reacting a mixture of 2-azidoethyl β-l-fucopyranoside (FucEtN3) and 2-azideoethyl β-d-glucopyranoside (GlcEtN3) with poly(propargyl methacrylate)-block-poly(n-butyl acrylate) (PPMA-b-PBA) using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Five block copolymers were obtained ranging from 100 mol % fucose to 100% glucose functionalization. The resulting micelles had hydrodynamic diameters of around 30 nm. In this work, we show that fucosylated micelles reveal an increased uptake by pancreatic, lung, and ovarian carcinoma cell lines, whereas the uptake by the healthy cell lines (CHO) is negligible. This finding suggests that these micelles can be used for targeted drug delivery toward cancer cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4PY00802B
Abstract: Inspired by the Ringsdorf model, statistical copolymers with solubility enhancers, platinum drugs and groove binders were compared.
Publisher: American Chemical Society (ACS)
Date: 26-02-2014
DOI: 10.1021/MA402078D
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.BIOMATERIALS.2011.08.091
Abstract: Cell-derived extracellular matrix (ECM) scaffolds have received considerable interest for tissue engineering applications. In this study, ECM scaffolds derived from mesenchymal stem cell (MSC), chondrocyte, and fibroblast were prepared by culturing cells in a selectively removable poly(lactic-co-glycolic acid) (PLGA) template. These three types of ECM scaffolds were used for in vitro cultures of MSC and fibroblasts to examine their potential as scaffolds for cartilage and skin tissue engineering. The MSC were cultured in MSC- and chondrocyte-derived ECM scaffolds. The ECM scaffolds supported cell adhesion, promoted both cell proliferation and the production of ECM and demonstrated a stronger stimulatory effect on the chondrogenesis of MSC compared with a conventional pellet culture method. Histological and immunohistochemical staining indicated that cartilage-like tissues were regenerated after the MSC were cultured in ECM scaffolds. Fibroblasts were cultured in the fibroblast-derived ECM scaffolds. Fibroblasts proliferated and produced ECM to fill the pores and spaces in the scaffold. After 2 weeks of culture, a uniform multilayered tissue was generated with homogenously distributed fibroblasts. Cell-derived ECM scaffolds have been demonstrated to facilitate tissue regeneration and will be a useful tool for tissue engineering.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.ACTBIO.2013.04.024
Abstract: Ideal biomaterials for bone tissue engineering should have the capability to guide the osteogenic differentiation of mesenchymal stem cells and, at the same time, to stimulate angiogenesis of endothelia cells. In this study it was found that three Ca-Mg-Si-containing bioceramics (bredigite Ca7MgSi4O16, akermanite Ca2MgSi2O7 and diopside CaMgSi2O6) had osteogenic and angiogenic potential. The effects of three silicate ceramics on the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and the angiogenesis of human aortic endothelial cells (HAECs) were explored in comparison with β-tricalcium phosphate (β-TCP) bioceramics. The proliferation, alkaline phosphatase (ALPase) activity and bone-related gene expression (COL1, ALPase, OP, BSP and OC) of hBMSCs were significantly enhanced upon stimulation with ionic extracts of these silicate bioceramics. In addition, the results showed that extracts from the three silicate bioceramics also stimulated HAEC proliferation and in vitro angiogenesis with improved NO synthesis and angiogenic gene expression (KDR, FGFR1, ACVRL1 and NOS3). Among the three silicate ceramics bredigite showed the highest osteogenic and angiogenic potential and with the highest extract Si (possibly Si(OH)3O(-)) concentration, while diopside had the lowest osteogenic and angiogenic potential with the lowest extract Si concentration. Furthermore, it was found that the concentration of Si ions in extracts of the three silicate bioceramics was obviously higher than that of β-TCP ceramics, indicating an important role of Si ions in stimulating cell proliferation, osteogenic differentiation and angiogenesis. The results suggest that the silicate-based akermanite and bredigite ceramics might be good scaffold biomaterials for bone tissue engineering applications due to their distinctive dual functions of osteogenesis/angiogenesis stimulation.
Location: China
Location: No location found
Start Date: 06-2015
End Date: 05-2018
Amount: $345,000.00
Funder: Australian Research Council
View Funded Activity