Targeting Hypoxic Tumor Plasticity for Recapturing Photodynamic‐Immunotherapy Sensitivity via Fluorinated Polysensitizers

作者：Lingpu Zhang, Lin Tang, Changyuan Yu, Haihua Xiao, Chaoyong Liu · 发表于：Advanced Functional Materials · 年份：2023 · DOI：10.1002/adfm.202310450 · 被引用次数：25 · 研究领域：Nanoplatforms for cancer theranostics、Cancer, Hypoxia, and Metabolism、Photodynamic Therapy Research Studies

Abstract Metabolic reprogramming is a key characteristics of tumor cells, mainly manifested by abnormal metabolism and tumor hypoxia. Here, the design of Poly FBODIPY characterized by the presence of BODIPY photosensitizers, fluorinated aliphatic chains as Oxygen affinity materials, and reactive oxygen species‐sensitive thioketal linkers is reported. Poly FBODIPY subsequently self‐assembles into NP@Poly FBODIPY which is capable of delivering oxygen and photosensitizers simultaneously and generating ROS under light irradiation, resulting in rapid polymer degradation and nanoparticle dissociation via breaking ROS‐sensitive thiol ketal linkers. NP@Poly FBODIPY can target hypoxic tumor plasticity to reprogram metabolism for recapturing photodynamic‐immunotherapy sensitivity for completely inhibiting tumor growth on multi‐drug‐resistant patient‐derived lung cancer xenografts (PDX MDR ). Moreover, NP@Poly FBODIPY ‐mediated photodynamic‐immunotherapy activates antitumor immune responses and effectively inhibits tumor growth and lung metastasis on an orthotropic metastatic triple‐negative breast cancer model. Mechanistically, metabolomics and lipidomics analysis reveals that NP@Poly FBODIPY ‐mediated photodynamic‐immunotherapy not only destroys the redox state of cancer cells, but also affects the metabolism of lipid, amino acid, and d ‐glutamine, thereby finally promoting autophagy and apoptosis and inhibiting the proliferation of cancer cells. These results highlight the potential ...