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.