还原响应性含硒纳米胶束的制备及其载药性能研究

Preparation and Drug-Loaded Performance of Reduction-Sensitive Nanomicelle with Selenium

以亲水性单甲氧基聚乙二醇(mPEG)与一端修饰有疏水性十六烷醇的3,3′-二硒代二丙酸(DSeDPA)通过酯化反应合成了两亲性聚合物mPEG-Se-Se-C_(16),以此为载体制备了负载抗癌药物阿霉素(DOX)的载药胶束,通过Raman光谱、FTIR和~1HNMR对中间体和聚合物结构进行表征。TEM、DLS和CMC分析发现胶束呈规则的圆球状,纳米载药胶束粒径为(198±5)nm(PDI=0.239),聚合物的临界胶束浓度为0.079 mg·mL^(-1)。载药胶束的包封率为51.92%,载药率为9.01%。药物释放和细胞毒性研究表明,基于二硒键的纳米载药胶束有显著的GSH敏感性,能将DOX快速、完全地释放出来,对肿瘤细胞具有精确的选择性和特异性,对正常细胞无明显毒性。

We synthesized the amphiphilic polymer mPEG-Se-Se-C16 by the esterification of methoxy polyethylene glycol（mPEG） and 3,3＇-diselanediyldipropanoic acid in which one end was modified with hydrophobic 1-hexadecanol. Moreover,we prepared DOX-loaded nanomicelle. Then we characterized the structures of intermediate and polymer by Raman spectrum, FTIR, and 1HNMR. The analyses of TEM, DLS, and CMC showed that micelles had regular ball shapes with particle size of （198 ± 5） nm（PDI= 0. 239）, and the critical micelle concentration of the polymer was 0. 079 mg . mL-1. The entrapment rate of DOX-loaded nanomicelle was 51.92 %, and drug-loaded rate was 9.01 %. Drug-release and cytotoxicity test showed that DOX-loaded nanomi- celle had significant GSH sensitivity, could release DOX quickly and completely, and had high selectivity and specificity to tumor cells, but no obvious toxicity to normal cells.