Macromolecular Nano‐Assemblies for Enhancing the Effect of Oxygen‐Dependent Photodynamic Therapy Against Hypoxic Tumors

Abstract In oxygen (O 2 )‐dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O 2 and subsequently generates cytotoxic singlet oxygen ( 1 O 2 ). Therefore, the availability of O 2 and the utilization efficiency of generated 1 O 2 are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of 1 O 2 resulting from its short half‐life and short diffusion distance significantly restrict the applicability of PDT for hypoxic tumors. To address these challenges, numerous macromolecular nano‐assemblies (MNAs) have been designed to relieve hypoxia, utilize hypoxia or enhance the utilization efficiency of 1 O 2 . Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O 2 ‐dependent PDT against hypoxic tumors.