Low Molecular Weight PEI-Based Vectors via Acid-Labile Ortho Ester Linkage for Improved Gene Delivery.
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 (≈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.
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Lei
L
Zhang
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Min
M
Yu
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Jun
J
Wang
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Rupei
R
Tang
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Guoqing
G
Yan
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Weijing
W
Yao
Engineering Research Center for Biomedical Materials, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province, 230601, P. R. China.
Xin
X
Wang
D002021:Buffers; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D016923:Cell Death; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004952:Esters / Q000737:chemistry*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010316:Particle Size; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D055672:Static Electricity; D014162:Transfection
D002021:Buffers; D004952:Esters; D011094:Polyethyleneimine; D004247:DNA
ortho ester; poly(ethylenimine); transfection