A Hypoxia‐Activatable Prodrug for Targeted Combination Therapy of Hepatoma
Abstract
Abstract Precision medicine is characterized by high accuracy and safety, showing robust superiority and significant potential in clinical applications. Organelle‐targeting therapies are important tactics for precision medicine, allowing for efficient tumor treatment and reduced off‐target toxicity. Herein, a mitochondria‐targeting and hypoxia‐activatable nanoprodrug (POPZ NPs) is prepared. The N‐oxide groups of POPZ NPs can successfully target mitochondria and are reduced to tertiary amines by Cytochrome P450 enzymes (CYP450s), which are highly expressed in hypoxic tumors and located in the inner mitochondrial membranes. Biocompatible POPZ NPs can become cytotoxic and produce type‐I photodynamic activities and enhance photothermal properties after reduction by CYP450s. The tumor‐specific activatable prodrug reveals potent efficacy for tumor elimination without causing systemic toxicity. This work may provide a paradigm for achieving precision medicine as well as more convenient and feasible tumor combination therapy.
Article Details
Authors (6)
Hongyu Wang
School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering
Tao Zhang
Shaojin Lu
Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 P. R. China
Tingting Sun
Zhigang Xie
Xuesi Chen
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, No.5625, Renmin Street, Changchun, Jilin 130022, P. R. China