Light-controlled oxygen production and collection for sustainable photodynamic therapy in tumor hypoxia

Hypoxia exists in most malignant tumors and often contributes to therapy resistance, especially for aerobic treatments such as photodynamic therapy (PDT) and radiotherapy. Here, we developed a novel light-controlled sustainable PDT in which light was used to help photosynthetic microorganisms (Chlorella) produce oxygen, and perfluorocarbon was used to enrich oxygen around the photosensitizer for sustained oxygen supply. After light stops, Chlorella further acts as an adjuvant to promote dendritic cell (DC) activation, promoting the antitumor immune response. We showed that sustainable PDT could continuously provide oxygen for photosensitizers and avoid PDT-induced local hypoxia. More importantly, sustainable PDT also promoted the activation of DCs and amplified the antitumor immune effects. Therefore, this novel strategy provides an effective but simple method for improving PDT in both tumor hypoxia and normoxia, and enhancing the antitumor immunity may be a new anti-resistance strategy for treating patients with advanced-stage cancer.