Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China;; School of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, People's Republic of China.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China;
Regen Biomater. 2015 Sep;2(3):159-66. doi: 10.1093/rb/rbv011. Epub 2015 Aug 10.
Camptothecin (CPT)-based drugs always undergo the reversible, pH-dependent lactone ring-opening reaction, yielding the inactive but toxic carboxylate form. Self-assembly strategy provides an effective route for preserving their bio-stability. In this article, nano-sized self-assemblies from CPT-based antitumor drugs were simply built up by directly diluting the stock dimethylsulfoxide solutions of (S)-(+)-CPT, (S)-10-hydroxyl camptothecin and carboxylic CPT with water/phosphate-buffered saline solution. Because of their different molecular structures in A-ring or modification on the 20-OH group, CPT self-assembled into helical nano-ribbons, whereas 10-hydroxycamptothecin and carboxylic CPT self-aggregated into flat nano-ribbons and cylindric nano-rods, respectively. Attractively, the self-assembly of CPT-based drugs could occur within 1 min at a low concentration of 1 × 10(-5 )M. Adopting the J-type self-aggregation, self-assemblies were stable in aqueous solution and could effectively protect the CPT-based drugs from hydrolysis, which thereby kept their bioactivity for tumor therapy.
喜树碱（CPT）类药物通常经历可逆的、依赖 pH 值的内酯环开环反应，生成无活性但有毒的羧酸盐形式。自组装策略为保持其生物稳定性提供了有效的途径。在本文中，通过直接将（S）-（+）-CPT、（S）-10-羟基喜树碱和羧酸喜树碱的二甲基亚砜储备溶液稀释到水/磷酸盐缓冲盐溶液中，简单地构建了基于 CPT 的抗肿瘤药物的纳米级自组装体。由于它们在 A 环中的不同分子结构或在 20-OH 基团上的修饰，CPT 自组装成螺旋纳米带，而 10-羟基喜树碱和羧酸喜树碱分别自组装成扁平纳米带和圆柱纳米棒。引人注目的是，CPT 类药物的自组装可以在低浓度 1×10(-5)M 下 1 分钟内发生。采用 J 型自聚集，自组装在水溶液中稳定，可以有效地保护 CPT 类药物免受水解，从而保持其用于肿瘤治疗的生物活性。
