Strategic Design of Conquering Hypoxia in Tumor for Advanced Photodynamic Therapy.

Photodynamic therapy (PDT), with its advantages of high targeting, minimally invasive, and low toxicity side effects, has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment (TME) presents hypoxia due to the low oxygen (O 2 ) supply caused by abnormal vascularization in neoplastic tissues and high O 2 consumption induced by the rapid proliferation of tumor cells. The PDT process generally relies on the presence of O 2 , so the efficacy of PDT can be hampered by a hypoxic TME. To address this problem, researchers have been developing advanced nanoplatforms and strategies to enhance the therapeutic effect of PDT in tumor treatment. This review summarizes recent advanced PDT therapeutic strategies to against the hypoxic TME during the PDT treatment, thus enhancing PDT efficacy, including increasing O 2 content in TME through delivering O 2 to the tumors and in situ generations of O 2 ; decreasing the O 2 consumption during PDT by design of type I photosensitizers. To boost the PDT therapeutic effect, recent synergistically combination therapy of PDT and other therapeutic methods such as chemotherapy, photothermal therapy (PTT), immunotherapy, gas therapy is accounted by addressing the challenging problems of mono PDT in hypoxic environments, including tumor resistance, proliferation, and metastasis. Finally, we provide perspectives of the opportunities and challenges of PDT in future clinical research and translations. This article is protected by copyright. All rights reserved.