黄世文
目前主要研究方向为生物医用高分子材料,包括药物控释、基因载体、纳米生物材料等。
个性化签名
- 姓名:黄世文
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
- 职称:-
-
学科领域:
勘查地质学
- 研究兴趣:目前主要研究方向为生物医用高分子材料,包括药物控释、基因载体、纳米生物材料等。
黄世文:男,博士,武汉大学化学与分子科学学院教授、博士生导师。生物医用高分子材料教育部重点实验室副主任。1989年毕业于南京大学化学系,获学士学位;1992年于武汉大学化学系获硕士学位,留校从事教学科研工作。2002年于武汉大学化学与分子科学学院获理学博士学位。2000年8月-2002年2月公派赴新加坡Johns Hopkins Singapore Biomedical Center进行合作研究。2005年被聘为武汉大学教授、博士生导师。2008年入选教育部新世纪优秀人才支持计划。目前主要研究方向为生物医用高分子材料,包括药物控释、基因载体、纳米生物材料等。在Advanced Materials, Biomaterials, Small, Bioconjugate Chemistry, Biomacromolecules, Polymer, Macromolecular Bioscience等期刊发表论文40余篇,他人正面引用300次,先后获湖北省自然科学一等奖、二等奖各一次。
-
主页访问
1158
-
关注数
0
-
成果阅读
556
-
成果数
11
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评论
-
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评论
-
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评论
-
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评论
-
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评论
-
引用
【期刊论文】Synthesis and degradation of poly(beta-aminoester) with pendantprimary amine
黄世文, Jun Chen, Shi-Wen Huang*, Min Liu, Ren-Xi Zhuo*
Polymer 48(2007)675-681,-0001,():
-1年11月30日
Three poly(beta-aminoester)s with pendant primary amines were synthesized by Michael addition of N-Boc-protected diamine to 1,4-butanedioldiacrylate, followed by removal of N-Boc-protective group under anhydrous acidic conditions. The degradation rate of poly(beta-aminoester)s with pendant primary amines is dependant on their side-chain structures and pH value of incubation buffer. The degradation in basicenvironments is much faster than in acidic environments. The degradation of poly(beta-aminoester) with pendant primary amine involves intramolecular/intermolecular amidation and hydrolytic degradation. Under physiological conditions, the intramolecular/intermolecular amidation ofpoly(beta-aminoester) plays an important role in the polymer degradation. Polymers 1ae1c show significant buffer capacity at pH 4e10. Thecytotoxicity of polymer 1a is much higher than that of polymers 1b and 1c.
Poly(, beta-aminoester), , Pendant primary amine, Degradation
-
47浏览
-
0点赞
-
0收藏
-
0分享
-
240下载
-
0评论
-
引用
【期刊论文】In Vitro Gene Delivery Using Polyamidoamine Dendrimers witha Trimesyl Core†
黄世文, Xue-Qing Zhang, ‡, § Xu-Li Wang, ‡ Shi-Wen Huang, § Ren-Xi Zhuo, *, § Zhi-Lan Liu, §Hai-Quan Mao, | and Kam W. Leong*, ^
Biomacromolecules 2005, 6, 341-350,-0001,():
-1年11月30日
Polyamidoamine (PAMAM) dendrimer represents one of the most efficient polymeric gene carriers. Toinvestigate the effect of the core structure and generation of dendrimers on the complex formation andtransfection efficiency, a series of PAMAM dendrimers with a trimesyl core (DT) at different generations(DT4 to DT8) were developed as gene carriers and compared with the PAMAM dendrimers derived frompentaerythritol (DP) and inositol (DI). The minimal generation number of DTs at which the dendrimer hasenough amino group density to effectively condense DNA was higher (generation 6) than those of DPs andDIs (generation 5). DTs of generation 6 or higher condensed DNA into complexes with an average diameterranging from 100 to 300nm, but the 4th and 5th generations of DT (DT4 and DT5) formed only a severeaggregate with DNA. Interestingly, the DT6/pDNA complex was determined to be much smaller (100-300nm) than those prepared with DP5 or DI5 (>600 nm) at N/P ratios higher than 15. The optimal generationnumbers at which the dendrimers showed the highest transgene expression in COS-7 cells were 5 for DPsand DIs but 6 for DTs. The DT6/pDNAcomplex with smaller size mediated higher transgene expression inCOS-7 cells than those prepared with DP5 or DI5. The in vitro transfection efficiency of the DT dendrimersas evaluated in HeLa cells, COS-7 cells, and primary hepatocytes decreased in the order of DT6 > DT7 >DT8 > DT5 > DT4. The transfection mediated by DT6 was significantly inhibited by bafilomycin A1. Theacid-base titration curve for DT6 showed high buffer capacity in the pH range from 5.5 to 6.4 (pKa-6).This permits dendrimers to buffer the pH change in the endosomal compartment. However, the transfectionefficiency mediated by DT6 decreased significantly in the presence of serum in both HeLa cells and COS-7cells. The cytotoxicity of DTs evaluated in HeLa cells using the 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay showed a trend of increasing toxicity with the polymer generations. TheLD50 values of DT4 through DT8 were 628, 236, 79, 82, and 77 íg/mL, respectively, which were higherthan that of poly(ethyleneimide) (18 íg/mL) and poly(L-lysine) (28 íg/mL) in the same assay. With a lowercytotoxicity and versatility for chemical conjugation, these PAMAM dendrimers with a DT core warrantfurther investigation for nonviral gene delivery.
-
67浏览
-
0点赞
-
0收藏
-
0分享
-
105下载
-
0评论
-
引用
黄世文, Shi-Wen Huang, †, ‡ Jun Wang, § Peng-Chi Zhang, † Hai-Quan Mao, | Ren-Xi Zhuo, *, ‡ andKam W. Leong*, §
Biomacromolecules 2004, 5, 306-311,-0001,():
-1年11月30日
A nonionic and water-soluble polyphosphoester, poly(2-hydroxyethyl propylene phosphate) (PPE3), wassynthesized by chlorination of poly(4-methyl-2-oxo-2-hydro-1,3,2-dioxaphospholane), followed by esterificationwith 2-benzyloxyethanol and deprotection of the hydroxyl group by catalytic hydrogenation in thepresence of Pd-C. PPE3 degraded rapidly in PBS 7.4 at 37℃. The cytotoxicity and tissue compatibilityassays suggested good biocompatibility of PPE3 in vitro and in vivo. The expression of pVR1255 Lucplasmid in mouse muscle after intramuscular (i.m.) injection of DNA formulated with PPE3 solution insaline was enhanced up to 4-fold compared with that of naked DNA. These results suggest the potential ofthis polyphosphoester for naked DNA-based gene therapy. The advantages of this polymer design includethe biodegradability of the polyphosphoester and its structural versatility, which allows the fine-tuning ofthe physicochemical properties to optimize the enhancement of gene expression in muscle.
-
49浏览
-
0点赞
-
0收藏
-
0分享
-
80下载
-
0评论
-
引用
黄世文, Jun Wang a, b, Shi-Wen Huang a, Peng-Chi Zhang a, Hai-Quan Mao a, , Kam W. Leong a, ∗
International Journal of Pharmaceutics 265(2003)75-84,-0001,():
-1年11月30日
Cationic polyphosphoesters (PPEs) with different side-chain charge groups were designed and synthesized as biodegradablegene carriers. Poly(N-methyl-2-aminoethyl propylene phosphate) (PPE-MEA), with a secondary amino group (-CH2CH2NHCH3)side chain released DNA in several hours at N/P (amino group of polymer to phosphate group of DNA) ratios from 0.5 to 5;whereas PPE-HA, bearing-CH2(CH2)4CH2NH2 groups in the side chain, did not release DNA at the same ratio range for 30days. Hydrolytic degradation and DNA binding results suggested that side chain cleavage, besides the polymer degradation,was the predominant factor affected the DNA release and transfection efficiencies. The side chain of PPE-MEA was cleavedfaster than that of PPE-HA, resulting poor cellular uptake and no transgene expression for PPE-MEA/DNA complexes in COS-7cells at charge ratios from 4 to 12. In contrast, PPE-HA/DNA complexes were stable enough to be internalized by cells andeffected gene transfection (3400 folds higher than background at a charge ratio of 12). Interestingly, gene expression levelsmediated by PPE-MEA and PPE-HA in mouse muscle following intramuscular injection of complexes showed a reversed order:PPE-MEA/DNA complexes mediated a 1.5–2-fold higher luciferase expression in mouse muscle as compared with naked DNAinjection, while PPE-HA/DNA complexes induced delayed and lowered luciferase expression than naked DNA. These resultssuggested that the side chain structure is a crucial factor determining the mechanism and kinetics of hydrolytic degradation ofPPE carriers, which in turn influenced the kinetics of DNA release from PPE/DNA complexes and their transfection abilities invitro and in vivo.
Non-viral gene delivery, Sustained release, Polymeric carrier, Polyphosphoester
-
39浏览
-
0点赞
-
0收藏
-
0分享
-
75下载
-
0评论
-
引用
【期刊论文】Recent progress in polymerbasedgene delivery vectors
黄世文, HUANG Shiwen & ZHUO Renxi
Chinese Science Bulletin 2003 Vol. 48 No.13 1304 1309,-0001,():
-1年11月30日
The gene delivery system is one of the threecomponents of a gene medicine, which is the bottle neck ofcurrent gene therapy. Nonviral vectors offer advantages overthe viral system of safety, ease of manufacturing, etc. As importantnonviral vectors, polymer gene delivery systemshave gained increasing attention and have begun to showincreasing promising. In this review, the fundamental andrecent progress of polymer-based gene delivery vectors isreviewed.
gene delivery,, gene transfer,, gene therapy,, polymer vector,, nonviral vector.,
-
37浏览
-
0点赞
-
0收藏
-
0分享
-
81下载
-
0评论
-
引用