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.

缺氧存在于大多数恶性肿瘤中，并且常常导致对治疗的抵抗，特别是对于有氧治疗，例如光动力疗法（PDT）和放射疗法。在这里，我们开发了一种新型的光控可持续PDT，其中光被用来帮助光合微生物（Chlorella）产生氧气，而全氟化碳被用来富集光敏剂周围的氧气以持续提供氧气。光停止后，小球藻进一步充当佐剂以促进树突状细胞（DC）活化，从而促进抗肿瘤免疫反应。我们表明，可持续的PDT可以持续为光敏剂提供氧气，避免PDT引起的局部缺氧。更重要的是，可持续的PDT还促进了DC的活化并增强了抗肿瘤免疫作用。因此，该新策略提供了一种有效但简单的方法来改善肿瘤缺氧和常氧时的PDT，并且增强抗肿瘤免疫力可能是治疗晚期癌症患者的新抗性策略。