Camptothecin (CPT) is a potent and broad-spectrum anti-tumor drug, but its clinical application is limited due to its poor water solubility, toxicity, and low drug-loading potential. Different delivery protocols have been developed to optimize the therapeutic effects of CPT. In this study, CPT was modified into a dimer (CPT-Mal-CPT), in which two CPT molecules are connected by a reduction-responsive maleimide thioether bond. Moreover, biocompatible methoxy poly(ethylene glycol)- b -poly(ε-caprolactone) (mPEG–PCL)-loaded CPT-Mal-CPT nanoparticles were prepared to overcome the limits of CPT application. The power X-ray diffractometer (PXRD) results indicate low crystallinity and amorphous nature of CPT-Mal-CPT. The CPT-Mal-CPT-loaded micelles showed a drug-loading content of 9.6% and a drug-loading efficiency of 56%. In addition, dimeric CPT micelles showed reduction-responsive release under 10-mM dithiothreitol (DTT), while negligible CPT release was detected in the absence of DTT. MTT assay indicated that cytotoxicity of dimeric CPT micelle was similar to free CPT.

中文翻译：

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二聚喜树碱负载的 mPEG-PCL 纳米颗粒具有高载药量和还原反应性药物释放

喜树碱（CPT）是一种有效的广谱抗肿瘤药物，但由于其水溶性差、毒性大、载药量低等问题，其临床应用受到限制。已经开发了不同的递送方案来优化 CPT 的治疗效果。在这项研究中，CPT 被修饰成二聚体 (CPT-Mal-CPT)，其中两个 CPT 分子通过还原反应性马来酰亚胺硫醚键连接。此外，制备了生物相容性甲氧基聚（乙二醇）-b-聚（ε-己内酯）（mPEG-PCL）负载的 CPT-Mal-CPT 纳米粒子以克服 CPT 应用的限制。功率 X 射线衍射仪 (PXRD) 结果表明 CPT-Mal-CPT 具有低结晶度和无定形特性。负载CPT-Mal-CPT的胶束显示出9.6%的载药量和56%的载药效率。此外，二聚体 CPT 胶束在 10 mM 二硫苏糖醇 (DTT) 下表现出还原反应性释放，而在不存在 DTT 的情况下检测到可忽略不计的 CPT 释放。MTT分析表明二聚体CPT胶束的细胞毒性与游离CPT相似。