Modulation of tumor hypoxia and redox microenvironment using nanomedicines for enhanced cancer photodynamic therapy

Photodynamic therapy (PDT) that combines light and photosensitizers to induce generation of reactive oxygen species (ROS) for killing cancer cells has provided a promising strategy for cancer treatment. However, the hypoxic tumor microenvironment often compromises the PDT efficacy due to its oxygen dependence. In addition, the existence of high levels of glutathione (GSH) in the tumor microenvironment can resist the generated ROS and thus limits PDT efficacy. To address these issues, nanomedicines than can modulate tumor hypoxia and redox microenvironment have been designed and developed in recent years. These nanomedicines can achieve enhanced cancer PDT efficacy through carrying oxygen, producing oxygen, consuming GSH and/or inhibiting GSH generation in tumor microenvironment. In this review, we summarize the recent advances in tumor hypoxia and redox microenvironment-modulating nanomedicines for enhanced PDT. The design principles and working mechanisms of these nanomedicines to alleviate hypoxia and reduce GSH levels for enhanced PDT efficacy are first introduced in detail. A conclusion and outlook regarding the development of nanomedicines for enhanced PDT are then discussed.