Recent Advances of Tumor Microenvironment-Responsive Nanomedicines-Energized Combined Phototherapy of Cancers

Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc. In this review, we will introduce the merits of combining PTT with PDT, summarize the recent important progress of combined phototherapies and their combinations with the dominant tumor treatment regimen, chemotherapy based on smart nanomedicines sensitive to various TME stimuli with a focus on their sophisticated designs, and discuss the challenges and future developments of nanomedicine-mediated combined phototherapies.