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Redox-cleavable star cationic PDMAEMA by arm-first approach of ATRP as a nonviral vector for gene de
閱讀：287 發(fā)布時(shí)間：2015-1-28| 提 供 商 | 美國布魯克海文儀器公司 | 資料大小 | 1.8MB |
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In this work, we synthesized a star cationic polymer(s-PDMAEMA) consisting of cleavable poly[N,Nbis(
acryloyl) cystamine](PBAC) crosslinked core and poly(N,N-dimethyl-ethylamine methacrylate)
(PDMAEMA) arms by atomic transfer radical polymerization using one-pot ‘‘arm first’’ method. The
s-PDMAEMA that was degradable in a mimic intracellular redox environment was more efficient in
condensing DNA. It was shown that s-PDMAEMA achieved higher gene transfection levels relative to
their linear precursors and s-PDMAEMA200 with longer and more arms exhibited superior transfection
efficiencies and lower cytotoxicity compared to PEI25K. The buffer capacities were examined by acid–
base titration; the pH-dependent morphological evolution and enzyme stability of PDMAEMA/DNA
complexes were investigated by atomic force microscopy (AFM) and time-resolved fluorescence spectroscopy,
respectively. The results indicated that the star polymers exhibited a stronger buffering ability
than their linear precursors due to the increased inner osmotic pressure. By decreasing the pH from 7.4 to
5.0, the linear PDMEMA/DNA complexes became more compact; in contrast, s-PDMAEMA200/DNA
complex adopted a loose morphology due to the steric barrier of inter-arms and outward extension of
positively charged arms. Analysis of the fluorescence life times of free and intercalated ethidium bromide
unveiled more effective protection of DNA afforded by s-PDMAEMA. The effect of medium pH on the star
PDMAEMA systemwas smaller owing to the ability of densely tertiary amino groups along multiple arms
to absorb more protons, which was favorable for endosomolytic escape of complexes.