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

In oxygen (O)-dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O and subsequently generates cytotoxic singlet oxygen (O). Therefore, the availability of O and the utilization efficiency of generated O are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of O 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 O. Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O-dependent PDT against hypoxic tumors.