Journal
SCIENCE CHINA-CHEMISTRY
Volume 53, Issue 3, Pages 502-507Publisher
SCIENCE PRESS
DOI: 10.1007/s11426-010-0108-x
Keywords
gene delivery; shielding system; pH-sensitive; polyglutamate
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Funding
- National Natural Science Foundation of China [20604028, 50873102, 50733003, 20621140369]
- Ministry of Science and Technology of China [2007DFR5020]
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To increase the in vivo stability of polycation gene carriers, a pH-sensitive shielding system, gamma-benzyl L-glutamate-co-glutamate acid polymer (PGA(60) (60 refers to the molar ratio of glutamate acid in the polymer)), was synthesized and characterized. PGA(60) showed pH sensitivity at about pH 6.0. PGA(60) shielded the positive charge of DNA/PEI (1:1) complexes. Gel retardation assay showed that no DNA-strand exchange with PGA(60) occurred after PGA(60) was added to DNA/PEI complexes at different proportions. MTT cytotoxicity tests demonstrated that neither PGA(60) nor DNA/PEI/PGA(60) ternary complexes had cytotoxicity at the test concentration. The transfection efficiency was improved when the positive charge was partly shielded by PGA(60). Because of the charge repulsion between the surface of cells and ternary complex particles, there was almost no transfection efficiency when the zeta potential of ternary complexes turned to negative. Because of the suitable pH sensitive range, PGA(60) may be a potential shielding system for polycation gene carriers to be used in vivo.
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