A dandelion-like nanomedicine via hierarchical self-assembly for synergistic chemotherapy and photo-dynamic cancer therapy

• Published in: Nanomedicine 2023-04, Vol.49, p.102660-102660, Article 102660
• Main Authors: Liang, Binbin, Miao, Yuhang, Zhao, Liying, Fang, Lan, Deng, Dawei
• Format: Article
• Language: English
• Subjects: Camptothecin - chemistry; Camptothecin - pharmacology; Camptothecin - therapeutic use; Cell Line, Tumor; Dandelion-like; Glutathione; Host-guest interaction; Humans; Lipid-based vesicles; Nanomedicine; Nanoparticles - chemistry; Neoplasms - drug therapy; Prodrugs - chemistry; Self-assembly; Synergistic therapy
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2023.102660

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. A dandelion-like cRGDfk-CCPT-mCe6 nanomedicine co-delivering camptothecin (CPT) and chlorin e6(Ce6) demonstrates favorable GSH-responsive property and tumor targeting for synergistic chemotherapy and photo-dynamic therapy. [Display omitted]