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

Abstract

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome‐based nanoparticle (designated as LipoMB/CaO 2 ) with O 2 self‐sufficient property for dual‐stage light‐driven PDT is demonstrated to address this problem. Through a short time irradiation, 1 O 2 activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO 2 with H 2 O, resulting in accelerated O 2 production. Accelerated O 2 level further regulates hypoxic tumor microenvironment and in turn improves 1 O 2 generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO 2 to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side‐effect. The O 2 self‐sufficient LipoMB/CaO 2 nanoplatform with dual‐stage light manipulation is a successful attempt for PDT against hypoxic tumor.