Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.

The gelation time of Diels–Alder crosslinked HA/PEG hydrogels can be reduced to an appropriate level for cell encapsulation and survival. At the same time, the DA click reaction makes the gel highly resilient and resistant to cyclic compression loading, which biomimics native articular cartilage biomechanical functions.

Prodrug-nanoparticles turn the disadvantage of the aggregation-caused quenching effect into an advantage to promote dual-modality PR104A release. Besides, photodynamic therapy-induced hypoxia activates PR104A for high-efficiency synergistic therapy.