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Abstract Title:

Red light triggered photodynamic-chemo combination therapy using a prodrug caged by photosensitizer.

Abstract Source:

Eur J Med Chem. 2021 Apr 5 ;215:113251. Epub 2021 Feb 12. PMID: 33611187

Abstract Author(s):

Gan Xu, Hong-Xia Zhang, Xiao-Qiang Li, De-Chao Yang, Jian-Yong Liu

Article Affiliation:

Gan Xu

Abstract:

Development of the drug with high therapeutic efficacy and low toxicity is crucial to cancer ablation. In this study, we have demonstrated a red light-responsive prodrug BDP-TK-CPT by connecting the chemotherapeutic agent camptothecin with a boron dipyrromethene (BDP)-based photosensitizer via a reactive oxygen species (ROS)-labile thioketal chain. Since camptothecin is modified by a BDP-based macrocycle at the active site, the formed prodrug displays an extremely low toxicity in dark. However, upon illumination by red light, it can efficiently generate ROS leading to cell death by photodynamic therapy. Meanwhile, the ROS generated can destroy thioketal group to release free camptothecin which further results in local cell death by chemotherapy. The combined antitumor effects of the prodrug have been verified in HepG2, EC109, and HeLa cancer cells and mice bearing H22 tumors. This study may provide an alternative strategy for stimuli-responsive combination treatment of tumors by conjugation of ROS-activatable prodrugs with photosensitizing agents.

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