Polyhydroxylalkyleneamines: A class of hydrophilic cationic polymer-based gene transfer agents

作者: Xiang Gao , Ramalinga Kuruba , Krishnan Damodaran , Billy W Day , Dexi Liu

DOI: 10.1016/J.JCONREL.2009.03.012

关键词:

摘要: Abstract A new series of cationic polymers, poly[ N , -bis-(2-hydroxylpropyl) alkylalcoholamine- co -ethylenediamine] were synthesized by directly cross-linking several dichloro alkylating agents with ethylenediamine and its derivatives. Co-polymerization cystamine introduces biodegradable disulfide bonds to the polymer backbone. When tested on COS-1 cells, PHAs showed reduced cytotoxicity, broad DNA ratios, enhanced transfection activity that was 2–9-fold better than polyethylenimine. Comparison studies also revealed chemical physical parameters related biological activities these polymers. The length side chain groups affects both toxicity polymers; a group moderate size appeared be optimal for high low toxicity. Introduction backbone further polymer. Fractionated molecular weight ≥ 5000 Da equally effective but smaller polymers ineffective in transfection. This flexible synthesis route enables determination key structural could aid improvement polymer-based agents.

参考文章(31)
Thorsten Bieber, Hans-Peter Elsässer, Preparation of a low molecular weight polyethylenimine for efficient cell transfection. BioTechniques. ,vol. 30, pp. 74- 81 ,(2001) , 10.2144/01301ST03
Yong-Beom Lim, Sang-Oh Han, Han-Uk Kong, Yah Lee, Jong-Sang Park, Byeongmoon Jeong, Sung Wan Kim, Biodegradable Polyester, Poly[α-(4-Aminobutyl)-l-Glycolic Acid], as a Non-Toxic Gene Carrier Pharmaceutical Research. ,vol. 17, pp. 811- 816 ,(2000) , 10.1023/A:1007552007765
Mini Thomas, James J. Lu, Chengcheng Zhang, Jianzhu Chen, Alexander M. Klibanov, Identification of Novel Superior Polycationic Vectors for Gene Delivery by High-throughput Synthesis and Screening of a Combinatorial Library Pharmaceutical Research. ,vol. 24, pp. 1564- 1571 ,(2007) , 10.1007/S11095-007-9279-3
M. Thomas, A. M. Klibanov, Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 14640- 14645 ,(2002) , 10.1073/PNAS.192581499
J. Suh, H.J. Paik, B.K. Hwang, Ionization of Poly(ethylenimine) and Poly(allylamine) at Various pH′s Bioorganic Chemistry. ,vol. 22, pp. 318- 327 ,(1994) , 10.1006/BIOO.1994.1025
Sang-oh Han, Ram I. Mahato, Sung Wan Kim, Water-soluble lipopolymer for gene delivery. Bioconjugate Chemistry. ,vol. 12, pp. 337- 345 ,(2001) , 10.1021/BC000120W
Michael A. Gosselin, Wenjin Guo, Robert J. Lee, Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjugate Chemistry. ,vol. 12, pp. 989- 994 ,(2001) , 10.1021/BC0100455
M. Thomas, J. J. Lu, Q. Ge, C. Zhang, J. Chen, A. M. Klibanov, Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung Proceedings of the National Academy of Sciences of the United States of America. ,vol. 102, pp. 5679- 5684 ,(2005) , 10.1073/PNAS.0502067102
Akin Akinc, Robert Langer, Measuring the pH environment of DNA delivered using nonviral vectors: implications for lysosomal trafficking. Biotechnology and Bioengineering. ,vol. 78, pp. 503- 508 ,(2002) , 10.1002/BIT.20215