Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China.
College of Life Sciences, Yantai University, Yantai 264005, China.
Int J Biol Macromol. 2023 Aug 30;247:125849. doi: 10.1016/j.ijbiomac.2023.125849. Epub 2023 Jul 17.
Amphiphilic low molecular weight chitosan-lipoic acid (LC-LA) conjugates with different degrees of substitution (DS) of LA were synthesized by N, N'‑carbonyldiimidazole (CDI) catalysis to self-assemble into redox-sensitive micelles. Critical micelle concentration (CMC), size, zeta potential, biocompatibility and redox-sensitive behavior of blank micelles were investigated. The results indicated that blank micelles with low CMC, nanoscale size and positive zeta potential showed excellent biocompatibility and redox-sensitive behavior. Doxorubicin (Dox) loaded micelles were prepared by encapsulating Dox into blank micelles. The loading ability, trigger-release behavior, antitumor activity and cellular uptake of Dox loaded micelles were studied. The results demonstrated that Dox loaded micelles with superior loading ability exhibited redox-trigger behavior, strong antitumor activity and increased cellular uptake efficiency against A549 cell. Besides, the effect of DS of LA on above properties was estimated. An increase in DS of LA reduced the CMC and cumulative release amount of Dox, but improved the loading efficiency, antitumor activity, and cellular uptake of Dox loaded micelles, which resulted from stronger interaction of hydrophobic groups in micelles with the DS of LA increased. Overall, self-assembled LC-LA micelles with good biosecurity and redox-sensitive behavior hold promising application prospects in Dox delivery and improving cancer therapeutic effect of Dox.
两亲性低分子量壳聚糖-硫辛酸（LC-LA）缀合物通过 N，N' -碳二亚胺（CDI）催化合成，具有不同程度的 LA 取代度（DS），以自组装成氧化还原敏感的胶束。研究了空白胶束的临界胶束浓度（CMC）、粒径、Zeta 电位、生物相容性和氧化还原敏感行为。结果表明，具有低 CMC、纳米级粒径和正 Zeta 电位的空白胶束具有优异的生物相容性和氧化还原敏感行为。通过将阿霉素（Dox）包封到空白胶束中制备了 Dox 负载的胶束。研究了 Dox 负载胶束的载药能力、触发释放行为、抗肿瘤活性和细胞摄取。结果表明，具有优异载药能力的 Dox 负载胶束具有氧化还原触发行为、强抗肿瘤活性和增加的 A549 细胞摄取效率。此外，还估计了 LA 的 DS 对上述性质的影响。LA 的 DS 的增加降低了 Dox 的 CMC 和累积释放量，但提高了 Dox 负载胶束的载药效率、抗肿瘤活性和细胞摄取，这是由于胶束中疏水性基团与 DS 的相互作用增强。总的来说，具有良好生物安全性和氧化还原敏感行为的自组装 LC-LA 胶束在 Dox 递送和提高 Dox 的癌症治疗效果方面具有广阔的应用前景。
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