Visible Light-Triggered Precision SO2 Release from Polymeric Nanomedicine for Cancer Therapy

A number of polymeric sulfur dioxide (SO2)-releasing nanomedicines have demonstrated promise in cancer treatment by enabling controlled SO2 release, triggered by endogenous (redox) stimuli. However, the heterogeneous distribution of these endogenous stimuli across different organs presents a significant challenge to clinical translation. To overcome this limitation, developing SO2 donors that respond to exogenous triggers offers a promising strategy for therapeutic advancement. Herein, an exogenous stimuli-responsive strategy is presented for generating SO2 from a series of amphiphilic block copolymers (BCPx) under visible light irradiation (427 nm) in a biological environment, aiming to evaluate their potential for cancer therapy. The coumarin-based, water-soluble polymers form well-defined nanostructures (BCPxNs) in aqueous media, releasing 70-85% of the theoretical SO2 within 4 h. Moreover, the BCPxNs nanostructures exhibit self-reporting behavior upon SO2 release. In vitro cellular assays with BCP2Ns nanostructures demonstrate an enhanced antiproliferative effect in cervical carcinoma HeLa cells under visible light irradiation (427 nm), with an IC50 value of 0.3 mg mL(-1). Investigations using confocal microscopy and flow cytometry confirm SO2-induced cell death. Overall, this strategy underscores the potential of light-responsive polymeric SO2 donors with spatiotemporal control for cancer therapy.