【作者】 郑化； 尹亮泉； 张雪琼； 张红； 胡瑞； 殷以华； 邱彤； 熊雄； 王群；

【Author】 Hua Zheng;Liangquan Yin;Xueqiong Zhang;Hong Zhang;Rui Hu;Yihua Yin;Tong Qiu;Xiong Xiong;Qun Wang;School of Chemistry,Chemical Engineering and Life Sciences,Wuhan University of Technology;

【机构】 武汉理工大学化工与生命科学学院；

【摘要】 本文中设计合成了基于透明质酸的具有良好血液循环稳定性的靶向交联纳米粒,其中疏水的核心叠氮苄胺可发生光交联,巯基修饰的透明质酸壳通过可生物还原的二硫键交联,制备了载甲氨蝶呤的核-壳双交联纳米粒,并考察了载药纳米粒在含不同浓度的谷胱甘肽的缓冲溶液中的药物释放行为;测试空白纳米粒以及载药纳米粒对He La细胞的细胞毒性,同时研究透明质酸对细胞毒性的影响;观察HeLa细胞对荧光标记的核-壳双交联纳米粒的摄取行为,同时研究培养液中高浓度的透明质酸对细胞摄取行为的影响。用该交联纳米粒包载抗肿瘤药物可提高载药纳米粒在体循环中的稳定性,当载药纳米粒进入癌细胞后可快速释放药物,达到靶向治疗的目的。更多还原

【Abstract】 The purpose of the present study was to develop a robust and redox-sensitive nanocarrier based on amphiphilic hyaluronic acid nanoparticles,in which the hydrophobic core was crosslinked by photo-crosslinking and the hyaluronic acid shell was crosslinked via a bioreducible disulfide linkage.Dynamic light scatteringshowed that the shell and core crosslinked nanocarriers were obviously more stable than core crosslinked or non-crosslinked nanoparticles.In vitro methotrexate release assays showed that the methotrexate-loaded bioreducible hyaluronic acid nanoparticles greatly suppressed drug release in phosphate-buffered saline(p H 7.4) without or with 20 μM glutathione.In vitro anticancer activity tests showed that the inhibition rate of methotrexate-loaded nanoparticles in He La cells reached 94%.Cellular uptake studies suggested that the prepared nanoparticles were probably internalized into the cancer cells via receptor-mediated endocytosis.更多还原