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

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.