Journal
ADVANCED HEALTHCARE MATERIALS
Volume 2, Issue 3, Pages 481-489Publisher
WILEY
DOI: 10.1002/adhm.201200154
Keywords
biodegradability; gene vector; peptide; reducible polycation
Funding
- Ministry of Science and Technology of China [2011CB606202]
- National Natural Science Funds for Distinguished Young Scholar [51125014]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT1030]
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To overcome the critical barriers in gene delivery, a series of reducible polycations (RPCs) based on low molecular weight (LMW) peptides, i.e. PolyHK(6)H, PolyHK(6)H-mPEG(1), PolyHK(6)H-mPEG(2), and PolyHK(6)H-mPEG(3), with different poly(ethylene glycol) (PEG) contents, are synthesized and evaluated as nonviral gene vectors. All the RPCs exhibit lower cytotoxicity compared with 25 kDa polyethyleneimine (PEI) and PEGylated PEI (PEI-mPEG: PEI-mPEG(1), PEI-mPEG(2), and PEI-mPEG(3)). PolyHK(6)H-mPEG(1) and PolyHK(6)H-mPEG(2) can bind and condense plasmid deoxyribonucleic acid (pDNA) efficiently with a particle size of about 200 nm. Moreover, they display much higher transfection efficiency than that of 25 kDa PEI especially in serum-supplemented medium. Moreover, PolyHK(6)H-mPEG(1) has equal transfection efficiency with PEI-mPEG(1) which is optimal in the PEI-mPEG, but PolyHK(6)H-mPEG(1) exhibits significantly lower cytotoxicity than PEI-mPEG(1). This is attributed to the fact that inter-peptide disulfide bonds can increase the stability of RPCs/pDNA complexes in extracellular environment and thereafter cleave in cytoplasm to facilitate the release of pDNA in intracellular environment. The PEGylated RPCs demonstrate here improved intracellular gene transfer performance and will have great potential applications in vivo.
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