期刊
MACROMOLECULAR BIOSCIENCE
卷 16, 期 8, 页码 1175-1187出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201600071
关键词
ortho ester; poly(ethylenimine); transfection
资金
- Chinese Program for New Century Excellent Talents in Universities [NCET-11-0661]
- National Natural Science Foundation of China [21174054, 21004030, 51503001]
- Scientific Research Foundation for Returned Scholars from Ministry of Education of China
- Natural Science Foundation of Anhui Province of China [1408085MB26]
- Doctor Research Foundation of Anhui University of China [J10113190075]
- Academic and Technology Introduction Project of Anhui University of China [AU02303203]
A series of novel pH-sensitive gene delivery vectors (POEI 1, 2, and 3) are synthesized through Michael addition from low molecular weight PEI (LMW PEI) via acid-labile ortho ester linkage with terminal acrylates (OEAc) by various feed molar ratios. The obtained POEI 1 and POEI 2 can efficiently condense plasmid DNA into nanoparticles with size range of 200-300 nm and zeta-potentials of about +15 mV while protecting DNA from enzymatic digestion compared with POEI 3. Significantly, ortho ester groups of POEI main-chains can make an instantaneous degradation-response to acidic endosomal pH (approximate to 5.0), resulting in accelerated disruption of polyplexes and intracellular DNA release. MTT assay reveals that all POEIs exhibit much lower cytotoxicity in different cells than branched PEI (25 KDa). As expected, POEI 1 and POEI 2 perform improved gene transfection in vitro, suggesting that such polycations might be promising gene vectors based on overcoming toxicity-efficiency contradiction.
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