Photodynamic therapy (
PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due to the hypoxic nature characteristic of many solid
tumors,
PDT is frequently limited in
therapeutic effect. Moreover, the consumption of O2 during
PDT may further aggravate the
tumor hypoxic condition, which promotes
tumor proliferation,
metastasis, and invasion resulting in poor prognosis of treatment. Therefore, numerous efforts have been made to increase the O2 content in
tumor with the goal of enhancing
PDT efficacy. Herein, these strategies developed in past decade are comprehensively reviewed to alleviate tumor hypoxia, including 1) delivering exogenous O2 to
tumor directly, 2) generating O2 in situ, 3) reducing
tumor cellular O2 consumption by inhibiting respiration, 4) regulating the TME, (e.g., normalizing
tumor vasculature or disrupting
tumor extracellular matrix), and 5) inhibiting the
hypoxia-inducible factor 1 (HIF-1) signaling pathway to relieve tumor hypoxia. Additionally, the O2 -independent Type-I
PDT is also discussed as an alternative strategy. By reviewing recent progress, it is hoped that this review will provide innovative perspectives in new nanomaterials designed to combat
hypoxia and avoid the associated limitation of
PDT.