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已发表论文
阿霉素 (Doxorubicin) 加载、含有芳香亚胺 (aromatic imine) 的两亲性星状嵌段聚合物： 合成、自组装和药物递送
Authors Qiu L, Hong CY, Pan CY
Published Date May 2015 Volume 2015:10 Pages 3623—3640
DOI http://dx.doi.org/10.2147/IJN.S78355
Received 29 November 2014, Accepted 25 January 2015, Published 18 May 2015
Abstract: Redox- and pH-sensitive branched star polymers (BSPs),
BP(DMAEMA-co-MAEBA-co-DTDMA)(PMAIGP)ns, have been successively
prepared by two steps of reversible addition–fragmentation chain transfer
(RAFT) polymerization. The first step is RAFT polymerization of
2-(N,N-dimethylaminoethyl)methacrylate (DMAEMA) and
p-(methacryloxyethoxy)benzaldehyde (MAEBA) in the presence of divinyl monomer,
2,2'-dithiodiethoxyl dimethacrylate (DTDMA). The resultant branched polymers
were used as a macro-RAFT agent in the subsequent RAFT polymerization. After
hydrolysis of the BSPs to form BP(DMAEMA-co-MAEBA-co-DTDMA)(PMAGP)ns
(BSP-H), the anticancer drug doxorubicin (DOX) was covalently linked to
branched polymer chains by reaction of primary amine of DOX and aldehyde groups
in the polymer chains. Their compositions, structures, molecular weights, and
molecular weight distributions were respectively characterized by nuclear
magnetic resonance spectra and gel permeation chromatography measurements. The
DOX-loaded micelles were fabricated by self-assembly of DOX-containing BSPs in
water, which were characterized by transmission electron microscopy and dynamic
light scattering. Aromatic imine linkage is stable in neutral water, but is acid-labile;
controlled release of DOX from the BSP-H-DOX micelles was realized at pH values
of 5 and 6, and at higher acidic solution, fast release of DOX was observed. In
vitro cytotoxicity experiment results revealed low cytotoxicity of the BSPs and
release of DOX from micelles in HepG2 and HeLa cells. Confocal laser
fluorescence microscopy observations showed that DOX-loaded micelles have
specific interaction with HepG2 cells. Thus, this type of BSP micelle is an
efficient drug delivery system.
Keywords: RAFT polymerization, controlled release, doxorubicin, branched star polymer, pH-sensitive
Keywords: RAFT polymerization, controlled release, doxorubicin, branched star polymer, pH-sensitive
