胶束
自愈水凝胶
聚(N-异丙基丙烯酰胺)
低临界溶液温度
药物输送
共聚物
材料科学
临界胶束浓度
阿霉素
色谱中的热响应聚合物
化学工程
毒品携带者
自由基聚合
高分子化学
化学
聚合物
纳米技术
水溶液
有机化学
复合材料
高效液相色谱法
外科
工程类
化疗
医学
反相色谱法
作者
Min Liu,Xia Song,Yuting Wen,Jingling Zhu,Jun Li
标识
DOI:10.1021/acsami.7b12849
摘要
In this work, we have synthesized a thermoresponsive copolymer, alginate-g-poly(N-isopropylacrylamide) (alginate-g-PNIPAAm) by conjugating PNIPAAm to alginate, where PNIPAAm with different molecular weights and narrow molecular weight distribution was synthesized by atomic transfer radical polymerization. The copolymer dissolved in water or phosphate-buffered saline buffer solution at room temperature and formed self-assembled micelles with low critical micellization concentrations when the temperature increased to above their critical micellization temperatures. At higher concentration, that is, 7.4 wt % in water, the copolymer formed solutions at 25 °C and turned into thermosensitive hydrogels when temperature increased to the body temperature (37 °C). Herein, we hypothesized that the thermoresponsive hydrogels could produce self-assembled micelles with the dissolution of the alginate-g-PNIPAAm hydrogels in a biological fluid or drug release medium. If the drug was hydrophobic, the hydrogel eventually could release and produce drug-encapsulated micelles. In our experiments, we loaded the anticancer drug doxorubicin (DOX) into the alginate-g-PNIPAAm hydrogels and demonstrated that the hydrogels released DOX-encapsulated micelles in a sustained manner. The slowly released DOX-loaded micelles enhanced the cellular uptake of DOX in multidrug resistant AT3B-1 cells, showing the effect of overcoming the drug resistance and achieving better efficiency for killing the cancer cells. Therefore, the injectable thermoresponsive hydrogels formed by alginate-g-PNIPAAm and loaded with DOX turned into a smart drug delivery system, releasing DOX-encapsulated micelles in a sustained manner, showing great potential for overcoming the drug resistance in cancer therapy.
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