Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, PR China.
Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, PR China; Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, PR China.
Nanomedicine. 2023 Apr;49:102660. doi: 10.1016/j.nano.2023.102660. Epub 2023 Feb 4.
The synergistic effect of chemotherapy and photo-dynamic therapy (PDT) is an effective way to improve the efficiency of tumor treatment. However, most synergistic therapeutic drugs have poor water solubility and stability, so it is difficult to achieve high therapeutic effects while avoiding the severe side effects. Herein, a unique dandelion-like nanomedicine (named as cRGDfk-CCPT-mCe6) was successfully synthesized using Ce6-loaded amphiphilic β-cyclodextrins (β-CD) doped lipid-based vesicles as the core (receptacle) and β-CD modified camptothecin (CPT) pro-drug as the flyable dandelion seeds. The β-CD modified CPT pro-drug was introduced into the core vesicles in succession via host-guest interaction between inter-molecular β-CD and CPT, and cRGDfk peptides were further introduced as the outermost layer (stigma) to enhance the internalization into cancer cells. CPT interacted with β-CD through glutathione (GSH)-cleavable disulfide bonds, which led to drug release in glutathione-rich cancer cells, just as spread of dandelion seeds in the wind. GSH consumption further disrupted the intracellular redox homeostasis of cancer cells through combined action of Ce6 with light irradiation and the synergistic anti-tumor effect was thus achieved, resulting in apoptosis of cancer cells. Therefore, the nanomedicine provides a facile and versatile anti-tumor strategy, as well as a persistent anti-cancer effects.
化疗和光动力疗法（PDT）的协同作用是提高肿瘤治疗效率的有效方法。然而，大多数协同治疗药物的水溶性和稳定性较差，因此很难在避免严重副作用的同时实现高治疗效果。在此，成功合成了一种独特的蒲公英样纳米药物（命名为 cRGDfk-CCPT-mCe6），它使用负载 Ce6 的两亲性β-环糊精（β-CD）掺杂脂质体作为核（容器），以及 β-CD 修饰的喜树碱（CPT）前药作为可飞行的蒲公英种子。通过分子间β-CD 和 CPT 之间的主体-客体相互作用，β-CD 修饰的 CPT 前药依次被引入核囊泡中，并且进一步引入 cRGDfk 肽作为最外层（柱头）以增强对癌细胞的内化。CPT 通过谷胱甘肽（GSH）可裂解的二硫键与β-CD 相互作用，导致在富含谷胱甘肽的癌细胞中释放药物，就像蒲公英种子在风中扩散一样。GSH 消耗通过 Ce6 与光照射的联合作用进一步破坏了癌细胞的细胞内氧化还原稳态，从而实现了协同抗肿瘤作用，导致癌细胞凋亡。因此，该纳米药物提供了一种简便通用的抗肿瘤策略，以及持久的抗癌效果。
