已为您找到该学者11条结果 成果回收站
黄世文, Lin Peng a, Yuan Gao b, Ya-Nan Xue a, Shi-Wen Huang a, *, Ren-Xi Zhuo a
Biomaterials 31(2010)4467e4476,-0001,():
-1年11月30日
To design successful polymeric gene delivery vehicles with good biocompatibility and highly efficientgene transfer ability is one of the great scientific challenges in modern gene therapy. Poly(amidoamine)with pendant aminobutyl group (PAA-BA) has been proved to exhibit high transfection efficiency againstbone marrow stromal cells (BMSCs) in vitro. In this work, based on previous research, PAA-BA'sbiocompatibility including in vitro cytotoxicity determined by effect on BMSCs' morphology, viability,membrane damage and apoptosis/necrosis, and in vivo tissue compatibility determined by muscular andhepatic tissue response were further investigated in comparison to branched polyethylenimine (PEI)25 kDa. The results demonstrated that PAA-BA possess much better cytocompatibility than PEI, yieldingslight cell morphological change, high cell viability and mild effect on cell membrane damage as well asinducing less apoptotic/necrotic cells at optimal N/P ratio. PAA-BA also exhibited better tissue compatibility,reflected by no or less inflammatory response in the site of muscle injection at the same (0.03% w/v)or higher concentration (0.1% w/v) and no hepatic tissue morphological change with normal hepatocytes.We concluded that PAA-BA was promising and safe candidate for in vitro BMSCs gene delivery and hadpotential for in future in vivo gene therapy.
Poly(, amidoamine), Bone marrow stromal cell Gene delivery Biocompatibility Cytotoxicity Apoptosis
-
50浏览
-
0点赞
-
0收藏
-
0分享
-
121下载
-
0
-
引用
黄世文, Lin Peng, Min Liu, Ya-Nan Xue, Shi-Wen Huang*, Ren-Xi Zhuo*
Biomaterials 30(2009)5825-5833,-0001,():
-1年11月30日
Poly(amidoamine)s with pendant primary amine (polymer 1a-1c) were evaluated as in vitro non-viralgene delivery vectors for bone marrow stromal cells (BMSCs). The cytotoxicity of these poly(amidoamine)s, measured by MTT assay, increased with increasing length of side chain, however, they were lesstoxic than branched polyethylenimine (PEI) 25 kDa. Using pGL-3 and pEGFP-C1 as luciferase gene andgreen fluorescent protein (GFP) gene, among all polycations including polymer 1a-1c and PEI, polymer1b at optimal N/P ratio showed highest luciferase expression (1.92×108 RLU/mg protein) as well aspercentage of cells expressing GFP (29.01±2.33%). For all polycations, intracellular trafficking of Cy3-labelled plasmid DNA (pDNA) was similar. Fluorescent particles attached to cell membrane at 0.5h afteradding the polycation/DNA complexes, aggregated in cytoplasm after 2h, and then stayed around theperinuclear region after 4h. pDNA nuclear localization appeared at 4h post-transfection, but much morepDNA entered into nucleus at 24h. At high N/P ratio, polymer 1a-1c could deliver pDNA into 70-80% ofBMSCs after 24h transfection, however, labelled pDNA was observed in only 4-25% of cells at the sametime. Compared to PEI, polymer 1b showed comparable or even higher percentage of pDNA uptake andnuclear localization. We concluded that poly(amidoamine)s with pendant primary amine, especiallypolymer 1b, are new kind of promising candidates of less toxic and highly efficient non-viral genedelivery vectors for BMSCs.
Bone marrow stromal cell Gene delivery Poly(, amidoamine), Polyethylenimine Intracellular trafficking Nuclear localization
-
53浏览
-
0点赞
-
0收藏
-
0分享
-
131下载
-
0
-
引用
【期刊论文】Poly(_-aminoester)s with Pendant Primary Amines for Efficient GeneDelivery
黄世文, Min Liu, Jun Chen, Ya-Nan Xue, Wen-Ming Liu, Ren-Xi Zhuo, and Shi-Wen Huang*
Bioconjugate Chem. 2009, 20, 2317-2323,-0001,():
-1年11月30日
Three hydrolytically degradable poly(_-aminoester)s containing ester bonds in the main chain and primary aminesin the side chain, synthesized by Michael polyaddition, were applied to deliver foreign DNA into cells in Vitro.These linear polycations can condense DNA into small-sized particles with positive surface charge at high N/Pratios. Their high buffer capacity at pH 5-7 facilitated the escape of DNA from the endosome and resulted inefficient gene expression. Under the optimal conditions, poly(_-aminoester)s with a pendant aminoethyl group(1a) showed higher transfection efficiencies than branched poly(ethylenimine) (PEI) 25KDa in 293T cells. Theeffect of side chain structure of the poly(_-aminoester) on transfection efficiency has been investigated, whichindicated that the poly(_-aminoester) containing the pendant aminoethyl group was the most efficient carrier forboth of 293T cells and COS-7 cells. The combination of hydrolytical degradation, high buffer capacity, relativelylow cytotoxicity, and high transfection efficiency suggested that this kind of poly(_-aminoester)s are novel promisingnonviral gene carriers.
-
56浏览
-
0点赞
-
0收藏
-
0分享
-
122下载
-
0
-
引用
黄世文, Min Zhang, Min Liu, Ya-Nan Xue, Shi-Wen Huang, * and Ren-Xi Zhuo*
Bioconjugate Chem. 2009, 20, 440-446,-0001,():
-1年11月30日
Polyaspartamide-based oligo-ethylenimine brushes (PASP-EDA, PASP-TEPA, PASP-PEHA, and PASP-PEI 423)were synthesized from polysuccinimide (PSI) via a ring-opening reaction with N-Boc protected ethylenediamine,tetraethylenepentamine, pentaethylenehexamine, and linear polyethylenimine (Mn 423), respectively. PASP-TEPA,PASP-PEHA, and PASP-PEI 423 possess high buffer capacity between pH 5 and pH 7, which is comparable tothat of branched PEI 25000. The cytotoxicity assay indicated that they all are less toxic than PEI 25000. At anN/P ratio of above 2, all of the four synthetic polycation brushes can condense plasmid DNA to form small sized(160-400nm) polyelectrolyte complexes with positive surface charge. The transfection of HEK 293 cells witholigo-ethylenimine brush/pRE Luc polyplexes indicated that the transfection efficiencies increased with increasingthe length of oligo-ethylenimine side chains. The luciferase expression with PASP-PEHA and PASP-PEI 423were as high as or even a little higher than that of PEI 25000. The results demonstrate that polyaspartamidebasedoligo-ethylenimine brushes are a very promising class of novel polycations for highly efficient and lesstoxic gene delivery.
-
99浏览
-
0点赞
-
0收藏
-
0分享
-
162下载
-
0
-
引用
黄世文, Ya-Nan Xue, Zhen-Zhen Huang, Jian-Tao Zhang, Min Liu, Min Zhang, Shi-Wen Huang*, Ren-Xi Zhuo*
Polymer 50(2009)3706-3713,-0001,():
-1年11月30日
An amphiphilic diblock copolymer of poly(acrylic acid-b-DL-lactide) (PAAc-b-PDLLA) was synthesized byring-opening polymerization of DL-lactide initiated by hydroxyl-terminated polyacrylic acid (PAAc-OH).The critical micelle concentration (CMC) of PAAc-b-PDLLA in aqueous solution, determined by fluorescencespectroscopy using pyrene as a probe, was found about 80 mg L_1. A solution of PAAc-b-PDLLA intetrahydrofuran (THF) was dialyzed against pure water to form pH-responsive micelles. Transmissionelectron microscopy (TEM) measurement showed that the micelles exhibited regular sphericalmorphology and the diameters of particles were in the range from 40 to 90 nm. The micelles were stableat a pH above 3 or at an ionic strength below 1.0, however, they aggregated and precipitated in thesolutions when further decreasing pH or increasing ionic strength. Prednisone acetate, as a modelhydrophobic drug, was loaded into the polymeric micelles. In vitro release of prednisone acetate frompolymeric micelles showed that the release kinetics was strongly pH-dependent. Hydrophobic drugdisplayed "burst" release at pH 7.4, while only a small part of loaded drug released at pH 1.4. Thisprovides a new choice to design delivery system for the gastrointestinal tract (GI tract), where the pHenvironment is strongly acidic in stomach and basic in intestine. The cytotoxicity measurement by MTTassay indicated that PAAc-b-PDLLA was low toxic in HeLa cells with an IC50 value of 2.8 mg mL_1, whichsuggests that PAAc-b-PDLLA could be used as a safe candidate for pH-responsive drug delivery.
Amphiphilic diblock copolymerpH-responsive micelleDrug delivery
-
26浏览
-
0点赞
-
0收藏
-
0分享
-
218下载
-
0
-
引用