Synthesis of biodegradable cross-linked poly(beta-amino ester) for gene delivery and its modification, inducing enhanced transfection efficiency and stepwise degradation.
Biodegradable cross-linked poly(beta-amino ester) (CLPAE) was synthesized by Michael addition of pentaerythritol triacrylate and N,N-dimethylethylenediamine and modified with aminohexanoic acid and lysine to CLPAE-Ahx and CLPAE-Lys, respectively, for a gene delivery system. They could self-assemble with plasmid DNA, forming nanosized polyplexes, and CLPAE-Ahx polyplex released plasmid DNA slowly during a week through stepwise degradation. The polymers showed minimal cytotoxicity on 293 cells due to their biodegradability and biocompatibility. Transfection efficiencies of CLPAE-Ahx and CLPAE-Lys were comparable to that of PEI in 293 cells and C2C12 cells. Additionally, high transfection of CLPAE-Ahx on primary rat aorta vascular smooth muscle cells (SMC) and primary mouse embryonic fibroblast cells (MEF) shows a potential for a gene delivery system on primary cells, restenosis treatment of human SMC, and MEF cell function research. In conclusion, CLPAE-Ahx could be used as a nontoxic and highly efficient gene delivery system.
Kim
Tae-Il
TI
School of Chemistry & Molecular Engineering, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, Korea.
Seo
Hyo Jung
HJ
Choi
Joon Sig
JS
Yoon
Jae Keun
JK
Baek
Jung-Un
JU
Kim
Kwan
K
Park
Jong-Sang
JS
D000586:Amination; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D001673:Biodegradation, Environmental; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000737:chemistry; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D014162:Transfection / Q000295:instrumentation* / Q000379:methods*
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004952:Esters; D011108:Polymers; D004247:DNA; D008239:Lysine