pH-Responsive PDMS-b-PDMAEMA Micelles for Intracellular Anticancer Drug Delivery

pH-Responsive PDMS-b-PDMAEMA Micelles for Intracellular Anticancer Drug Delivery
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DOI:
10.1021/bm500919z
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发表时间:
2014-09-01
期刊:
影响因子:
6.2
通讯作者:
Meier, Wolfgang
Meier, Wolfgang
中科院分区:
化学2区
文献类型:
--
作者:
Car, Anja;Baumann, Patric;Meier, Wolfgang

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采用原子转移自由基聚合法合成了一系列聚甲基丙烯酸甲酯(poly(dimethysiloxane)-b-poly(2-(dimethylamino)ethyl-b-PDMAEMA)嵌段共聚物。在水溶液中,聚合物自组装成直径在80至300 nm之间的胶束,具有包裹DOX的能力。PDMAEMA嵌段最短(5个单位)的聚合物显示出良好的细胞活力,而含有较长PDMAEMA嵌段长度(13和22个单位)的胶束会导致细胞毒性增加。载体释放DOX作为对pH从7.4下降到5.5的反应。激光共聚焦扫描显微镜(CLSM)显示,纳米颗粒被内吞作用带入酸性细胞室。此外,随着细胞形态和药物释放的变化,负载DOX的纳米载体在24小时内表现出细胞内的pH响应。
A series of poly(dimethysiloxane)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMS-b-PDMAEMA) block copolymers were synthesized with atom transfer radical polymerization (ATRP). In aqueous solution the polymers self-assembled into micelles with diameters between 80 and 300 nm, with the ability to encapsulate DOX. The polymer with the shortest PDMAEMA block (5 units) displayed excellent cell viability, while micelles containing longer PDMAEMA block lengths (13 and 22 units) led to increased cytotoxicity. The carriers released DOX in response to a decrease in pH from 7.4 to 5.5. Confocal laser scanning microscopy (CLSM) revealed that nanoparticles were taken up by endocytosis into acidic cell compartments. Furthermore, DOX-loaded nanocarriers exhibited intracellular pH-response as changes in cell morphology and drug release were observed within 24 h.