Dual-Stage Light Amplified Photodynamic Therapy against Hypoxic Tumor Based on an O₂ Self-Sufficient Nanoplatform

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome-based nanoparticle (designated as LipoMB/CaO₂ ) with O₂ self-sufficient property for dual-stage light-driven PDT is demonstrated to address this problem. Through a short time irradiation, ¹ O₂ activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO₂ with H₂ O, resulting in accelerated O₂ production. Accelerated O₂ level further regulates hypoxic tumor microenvironment and in turn improves ¹ O₂ generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO₂ to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side-effect. The O₂ self-sufficient LipoMB/CaO₂ nanoplatform with dual-stage light manipulation is a successful attempt for PDT against hypoxic tumor.