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

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.