卡铂@葡聚糖纳米载体的自组装/聚合一步法制备及生物应用  

One-step Self-assembly/polymerization Fabrication and Biomedical Application of Carboplatin@ Dextran Nanocarrier

作　　者：高苗苗 王成龙 窦红静[1] 许国雄 GAO Miaomiao;WANG Chenglong;DOU Hongjing;XU Guoxiong(State Key Laboratory of Metal Matrix Composites,School of Materials Science and Engineering,Shanghai Jiao Tong University,Shanghai 200240,China;Central Laboratory,Jinshan Hospital of Fudan University,Shanghai 201508,China)

机构地区：[1]上海交通大学材料科学与工程学院,金属基复合材料国家重点实验室,上海200240 [2]复旦大学附属金山医院中心实验室,上海201508

出　　处：《高等学校化学学报》2019年第6期1301-1309,共9页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21871180,81872121);上海市“科技创新行动计划”基础研究领域项目(批准号:18JC1413500);上海高校特聘教授(东方学者)计划(批准号:SHDP201802);上海市教委“曙光计划”(批准号:12SG12)资助~~

摘　　要：在接枝共聚辅助自组装(GISA)制备葡聚糖纳米载体的过程中,利用丙烯酸单体与卡铂之间的非共价键作用,使得卡铂参与到葡聚糖纳米载体的形成中,从而一步实现了卡铂@葡聚糖纳米载体的制备,并使用肿瘤还原性环境敏感的二硫键来交联纳米载体,得到了对肿瘤还原环境响应的纳米药物载体.对纳米药物载体的结构、粒径及形貌进行表征,结果显示,纳米药物载体粒径为(92±0.2) nm, Zeta 电位为(-8±0.3) eV.通过体外药物释放研究发现,在还原性环境中,载体可持续72 h释放药物,最大释放量达80%.细胞摄取实验表明负载卡铂的纳米药物载体可在4 h内高效地进入细胞核;其半抑制浓度(IC50)为25.32 μg/mL,达到和相同浓度游离卡铂相仿的促肿瘤细胞凋亡效果.此一步法所制备的卡铂@葡聚糖纳米载体具有良好的生物应用前景.We introduced disulfide bond in the crosslinking points of the carboplatin@ dextran to endow the reducing environmental sensitivity to the nanocarriers. Its structure, particle size and morphology of the nanocarrier were characterized by means of dynamic light scattering(DLS), 1 H NMR and FTIR. The results showed that the size of the nanocarrier was (92±0.2) nm. In vitro drug release studies disclosed that the carboplatin inside the nanocarrier can be released for 80% in 72 h in a reducing environment. The cell uptake experiments showed that the nanocarriers loaded with carboplatin could efficiently enter the cell nuclei within 4 h . The half maximal inhibitory concentration(IC50) of the carboplatin@dextran nanocarrier was 25.32 μg/mL , which had similar cytotoxicity to the free carboplatin at the same concentration. The above results demonstrate that carboplatin@dextran nanocarrier prepared by the one-step method has a good biomedical application prospect.

关 键 词：一步法 接枝聚合诱导自组装 卡铂@葡聚糖纳米载体 还原环境敏感 

分 类 号：O636.1[理学—高分子化学]