Sanger’s Reagent‐Mediated Prodrug for Light‐Controlled Release of Camptothecin With Fluorescent Indication

Stimuli-responsive prodrug system has emerged as an attractive approach to address the issues encountered by conventional chemotherapeutics. Among the growing arsenal of stimuli-responsive prodrug strategies, the photocaging approach occupies a privileged position because it replaces poorly controlled biological triggers with an external light stimulation, thereby offering a promising solution to the therapeutic limitations in cancer treatment. In this work, we have developed a Sanger's reagent based prodrug, Sanger-Naph-CPT, which enables light-controlled camptothecin (CPT) release in cancer cells via 400 nm light. Integrating a naphthalimide fluorescent reporter, the system allows real-time monitoring of drug release kinetics. The photocaged prodrug was characterized by HPLC/HRMS, confirming photodegradation under light. Confocal microscopy showed minimal baseline fluorescence in HeLa cells without irradiation, with robust fluorescence emerging postirradiation (intensity increasing with exposure time). MTT assays showed that, after light irradiation, Sanger-Naph-CPT exhibited dose-dependent cytotoxicity comparable to free CPT, demonstrating restored activity of released CPT. This dual-function platform combines light-triggered therapeutic activity and fluorescence reporting, offering a modular design for photocontrolled prodrugs.