A HCOF-Based Drug Delivery System for Cancer Therapy via Intracellular Click Chemistry.

Abstract

Click reactions exhibit remarkable selectivity within biological systems, making them powerful and useful tools for synthesizing various novel anticancer drugs in biomedical fields. Utilizing the overexpressed enzyme in a tumor microenvironment to trigger click reactions between nontoxic or low-toxicity precursors provides an effective solution to the high toxicity of conventional chemotherapeutic agents. However, small-molecule drugs tend to undergo rapid metabolism within biological environments; therefore, an effective drug delivery system was needed. In this study, a hollow covalent organic framework (HCOF) was introduced, prodrug molecules were loaded, and finally, an anticancer drug was formed via the click reaction with the help of nitroreductase (NTR). Both in vitro and in vivo studies confirmed the excellent antitumor efficacy of the resulting therapeutic platform. This work further expands the biomedical applications of HCOF via click chemistry.