10.1021/acsami.8b04301.s001
Bin Xu
Bin
Xu
Yuan-Jun Zhu
Yuan-Jun
Zhu
Cheng-Han Wang
Cheng-Han
Wang
Chong Qiu
Chong
Qiu
Jing Sun
Jing
Sun
Yi Yan
Yi
Yan
Xin Chen
Xin
Chen
Jian-Cheng Wang
Jian-Cheng
Wang
Qiang Zhang
Qiang
Zhang
Improved Cell Transfection of siRNA by pH-Responsive
Nanomicelles Self-Assembled with mPEG‑<i>b</i>‑PHis‑<i>b</i>‑PEI Copolymers
American Chemical Society
2018
extracellular acidic microenvironments
PHi
EHE copolymers
nanoplexe
pH-responsive EHE nanomicelles
pH-Responsive Nanomicelles Self-Assembled
pH-responsive disassembly
mPEG
Cell Transfection
HeLa cells
nanostructural disassembling
cationic nanomicelles
lysosomal acidic microenvironments
PEI
ECE
hydrodynamic diameter
cell internalization
expression levels
cell transfection
novel pH-responsive nanomicelles self-assembled
siRNA transfection
2018-06-08 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Improved_Cell_Transfection_of_siRNA_by_pH-Responsive_Nanomicelles_Self-Assembled_with_mPEG_i_b_i_PHis_i_b_i_PEI_Copolymers/6608918
Here, the novel pH-responsive
nanomicelles self-assembled with amphipathic meo-poly(ethylene glycol)-<i>b</i>-poly(l-histidine)-<i>b</i>-polyethylenimine
(mPEG-<i>b</i>-PHis-<i>b</i>-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-<i>b</i>-poly(ε-caprolactone)-<i>b</i>-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.