A series of novel water soluble chitosan derivatives as gene vectors was synthesized. The delivery systems were tested for their ability to form complexes with plasmid DNA by utilizing agarose gel electrophoresis, particle size analysis, zeta potential measurement and scanning electron microscopy. Furthermore, cytotoxicity of chitosan derivatives and transfection efifciency of polyplexes were evaluated in vitro. The experimental results showed that the novel chitosan derivatives had lower cytotoxicity, good DNA condensation, and higher transfection efifciencies compared to chitosan in both 293T and HeLa cell lines. It was indicated that these chitosan derivatives were promising candidates for non-viral gene vectors.
参考文献
| [1] | Dorothee VL;Hasselmann S;Hasselmann K .Gene Therapy for HIV Infection:What does It Need to Make It Work[J].Journal of Gene Medicine,2006,8:658-667. |
| [2] | Wong LF;Goodhead L;Prat C;Mitrophanous KA;Kingsman SM;Mazarakis ND .Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications.[J].Human gene therapy,2006(1):1-9. |
| [3] | Pawliuk R;Westerman KA;Fabry ME et al.Correction of Sickle Cell Disease in Transgenic Mouse Models by Gene Therapy[J].SCIENCE,2001,294:2368-2372. |
| [4] | Lehrman S .Virus Treatment Questioned after Gene Therapy Death[J].NATURE,1999,401:517-518. |
| [5] | Li S;Huang L .Non-viral Gene Therapy:Promises and Chall-enges[J].GENE THERAPY,2000,7:31-34. |
| [6] | Luo K;Li CX;Wang G et al.Peptide Dendrimers as Efifcient and Biocompatible Gene Delivery Vectors:Synthesis and in Vitro Characterization[J].Journal of Controlled Release,2011,155:77-87. |
| [7] | Merdan T;Kopecek J;Kissel T .Prospects for Cationic Poly-mers in Gene and Oligonucleotide Therapy Against Cancer[J].Advanced Drug Delivery Reviews,2002,54:715-758. |
| [8] | Pack DW;Hoffman AS;Pun S et al.Design and Development of Polymers for Gene Delivery[J].Nature Reviews Drug Discovery,2005,4:589-593. |
| [9] | He YY;Cheng G;Xie L et al.Polyethyleneimine/DNA Polyplexes with Reduction-sensitive Hyaluronic Acid Derivatives Shielding for Targeted Gene Delivery[J].BIOMATERIALS,2013,34:1235-1245. |
| [10] | Hu Y;Xu BH;Ji QX et al.A Mannosylated Cell-penetrating Peptide-graft-polyethylenimine as a Gene Delivery Vector[J].BIOMATERIALS,2014,35(13):4236-4246. |
| [11] | Wen YT;Pan SR;Luo X et al.PEG-and PDMAEG-Graft-Modified Branched PEI as Novel Gene Vector:Synthesis,Characterization and Gene Transfection[J].Biomaterials Science Polymer Edition,2010,21:1103-1126. |
| [12] | Layek B;Singh .Caproic Acid Grafted Chitosan Cationic Nanocomplexes for Enhanced Gene Delivery:Effect of Degree of Substitution[J].International Journal of Pharmaceutics,2013,447:182-191. |
| [13] | Morris VB;Sharma CP .Folate mediated histidine derivative of quaternised chitosan as a gene delivery vector.[J].International Journal of Pharmaceutics,2010(1/2):176-185. |
| [14] | Zhao XL;Li ZY;Pan HB et al.Enhanced Gene Delivery by Chitosan-disulfide-conjugated LMW-PEI for Facilitating Osteogenic Differentiation[J].ACTA BIOMATERIALIA,2013,9:6694-6703. |
| [15] | Ma D;Lin QM;Zhang LM et al.A Star-shaped Porphyrin-Arginine Functionalized poly(L-lysine)Copolymer for Photo-enhanced Drug and Gene Co-delivery[J].BIOMATERIALS,2014,35:4357-4367. |
| [16] | Sheng RL;Xia KJ;Chen J et al.Terminal Modification on mPEG-dendritic poly-(l)-lysine Cationic Diblock Copolymer for Efifcient Gene Delivery[J].Biomaterials Science Polymer Edition,2013,24:1935-1951. |
| [17] | Zhang X;Ma GH;Su ZG et al.Novel poly(L-lysine)Particles[J].Journal of Controlled Release,2011,152:182-184. |
| [18] | Mumper RJ;Wang JJ;Claspell JM et al.Novel Polymeric Condensing Carriers for Gene Delivery[J].International Journal of Nanomedicine,1995,22:178-179. |
| [19] | Du YZ;Liu P;Zhou JP et al.Stearic Acid Grafted Chitosan Oligosaccharide Micelle as a Promising Vector for Gene Delivery System:Factors Affecting the Complexation[J].International Journal of Pharmaceutics,2010,391:260-266. |
| [20] | Gao JQ;Zhao QQ;Lv TF et al.Gene-carried Chitosan-linked-PEI Induced High Gene Transfection Efficiency with Low Toxicity and Signiifcant Tumor-suppressive Activity[J].International Journal of Pharmaceutics,2010,387:286-294. |
| [21] | Liu G;Molas M;Grossmann GA et al.Biological Properties of poly-L-lysine-DNA Complexes Generated by Cooperative Binding of the Polycation[J].Gene Medicine,2001,276:34379-34387. |
| [22] | Strand SP;Lelu S;Reitan N .Molecular design of chitosan gene delivery systems with an optimized balance between polyplex stability and polyplex unpacking.[J].Biomaterials,2010(5):975-987. |
| [23] | Wang BQ;He CB;Tang C et al.Effects of Hydrophobic and Hydrophilic Modiifcations on Gene Delivery of Amphiphilic Chitosan Based Nanocarriers[J].BIOMATERIALS,2011,32:4630-4638. |
| [24] | Koping Hoggard M;Varum KM;Issa M;Danielsen S;Christensen BE;Stokke BT;Artursson P .Improved chitosan-mediated gene delivery based on easily dissociated chitosan polyplexes of highly defined chitosan oligomers.[J].Gene therapy,2004(19):1441-1452. |
| [25] | Liu W;Sun S;Cao Z;Zhang X;Yao K;Lu WW;Luk KD .An investigation on the physicochemical properties of chitosan/DNA polyelectrolyte complexes.[J].Biomaterials,2005(15):2705-2711. |
| [26] | Young Hyo Kim;Se Hoon Gihm;Chong Rae Park;Kuen Yong Lee;Tae Woo Kim;Ick Chan Kwon;Hesson Chung;Seo Young Jeong .Structural Characteristics of Size-Controlled Self-Aggregates of Deoxycholic Acid-Modified Chitosan and Their Application as a DNA Delivery Carrier[J].Bioconjugate Chemistry,2001(6):932-938. |
| [27] | Kean T;Roth S;Thanou M .Trimethylated chitosans as non-viral gene delivery vectors: Cytotoxicity and transfection efficiency[J].Journal of Controlled Release: Official Journal of the Controlled Release Society,2005(3):643-653. |
| [28] | Kim TH.;Ihm JE.;Choi YJ.;Nah JW.;Cho CS. .Efficient gene delivery by urocanic acid-modified chitosan[J].Journal of Controlled Release: Official Journal of the Controlled Release Society,2003(3):389-402. |
| [29] | Lu, Bo;Wang, Chang-Fang;Wu, De-Qun;Li, Cao;Zhang, Xian-Zheng;Zhuo, Ren-Xi .Chitosan based oligoamine polymers: Synthesis, characterization, and gene delivery[J].Journal of Controlled Release: Official Journal of the Controlled Release Society,2009(1):54-62. |
| [30] | Lu B;Xu XD;Zhang XZ et al.Low Molecular Weight Polyethylenimine Grafted N-Maleated Chitosan for Gene Delivery:Properties andin vitro Transfection Studies[J].Biomacromolecules,2008,9:2594-2600. |
| [31] | Smith PK;Krohn RI;Hemanson GT et al.Measurement of protein using bicinchoninic acid[J].Analytical Biochemistry,1985,150:76-85. |
| [32] | Yemin Liu;Theresa M.Reineke .Hydroxyl Stereochemistry and Amine Number within Poly(glycoamidoamine)s Affect Intracellular DNA Delivery[J].Journal of the American Chemical Society,2005(9):3004-3015. |
| [33] | Nomura T;Nakjima S;Kawabata K et al.Intratumoral Pharmacokinetics andin vivo Gene Expression of Naked Plasmid DNA and Its Cationic Liposome Complexes after Direct Gene Transfer[J].Cancer Research,1997,57:2681-2686. |
| [34] | Kunath K.;von Harpe A.;Fischer D.;Peterson H.;Bickel U.;Voigt K. Kissel T. .Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine[J].Journal of Controlled Release: Official Journal of the Controlled Release Society,2003(1):113-125. |
| [35] | Choksakulnimitr S;Masuda S;Tokuda H et al.In Vitro Cytotoxicity of Macromolecules in Different Cell Culture Systems[J].Journal of Controlled Release,1995,34:233-241. |
| [36] | Fischer D.;Li YX.;Ahlemeyer B.;Krieglstein J.;Kissel T. .In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.[J].Biomaterials,2003(7):1121-1131. |
上一张
下一张
上一张
下一张
计量
- 下载量()
- 访问量()
文章评分
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%