am8b04301_si_001.pdf (1.31 MB)
Improved Cell Transfection of siRNA by pH-Responsive Nanomicelles Self-Assembled with mPEG‑b‑PHis‑b‑PEI Copolymers
journal contribution
posted on 2018-06-08, 00:00 authored by Bin Xu, Yuan-Jun Zhu, Cheng-Han Wang, Chong Qiu, Jing Sun, Yi Yan, Xin ChenXin Chen, Jian-Cheng Wang, Qiang ZhangHere, the novel pH-responsive
nanomicelles self-assembled with amphipathic meo-poly(ethylene glycol)-b-poly(l-histidine)-b-polyethylenimine
(mPEG-b-PHis-b-PEI, EHE) copolymers
based on hydrophobic interaction of PHis with deprotonation of imidazoles
were developed for siRNA transfection. The cationic nanomicelles could
electrostatically compact siRNA into stable EHE/siRNA nanoplexes with
a hydrodynamic diameter of ∼190 nm and present a low toxicity
in normal physiological condition (pH ∼ 7.4). Different from
pH-irresponsive ECE/siRNA nanoplexes based on mPEG-b-poly(ε-caprolactone)-b-PEI (ECE), the EHE/siRNA
nanoplexes exhibited a higher cellular uptake along with an increased
ζ-potential (from +18 to +32 mV) when the pH changed from 7.4
to 6.8 (extracellular acidic microenvironments). After cell internalization,
the EHE/siRNA nanoplexes also exhibited an enhanced nanostructural
disassembling and release of siRNA from lysosomal acidic microenvironments
(pH ∼ 5.5). Furthermore, it was demonstrated that the EHE/siEGFR
nanoplexes downregulated the expression levels of the corresponding
mRNA and protein more efficiently than ECE/siEGFR in HeLa cells. The
improved siRNA silencing effects of EHE/siEGFR nanoplexes resulted
from the higher cellular uptake and enhanced endosomal/lysosomal escape,
which is associated with the pH-responsive disassembly of nanostructure
as well as the synergistic “proton sponge” effects of
PHis and PEI in EHE copolymers. Therefore, the pH-responsive EHE nanomicelles
would be promising and potential carriers for cell transfection of
siRNA.
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extracellular acidic microenvironmentsPHiEHE copolymersnanoplexepH-responsive EHE nanomicellespH-Responsive Nanomicelles Self-AssembledpH-responsive disassemblymPEGCell TransfectionHeLa cellsnanostructural disassemblingcationic nanomicelleslysosomal acidic microenvironmentsPEIECEhydrodynamic diametercell internalizationexpression levelscell transfectionnovel pH-responsive nanomicelles self-assembledsiRNA transfection
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