Photodynamic-based combinatorial cancer therapy strategies: Tuning the properties of nanoplatform according to oncotherapy needs

In recent years, the wide application of photodynamic therapy (PDT) in the field of biomedicine has proved its significance in cancer treatment. A variety of nanomaterials are employed in PDT to transfer the received energy to photosensitizer for the generation of toxic singlet oxygen (¹O₂) to eliminate cancer cells, which has advantages of tissue specificity, non-invasiveness, and low toxicity. However, the low penetration of the light source, the hypoxia of the tumor microenvironment (TME), and the metastasis and recurrence of tumor cells severely limit the therapeutic effect of PDT. In this review, the design of PDT platforms used for oncotherapy is presented, starting with the principle of PDT. Additionally, this review discusses the latest studies of PDT-based combinatorial cancer therapy strategies in the process of tumor treatment, aiming to evaluate the potential of PDT in future clinical cancer treatments. Specifically, the latest progress of using combination therapy strategies to improve PDT's main deficiencies in three aspects are reviewed: i) combined with a few drugs or gases to overcome hypoxic TME, ii) employing advanced light sources to increase penetration depth, iii) combined with immunotherapy (IT) to inhibit tumor metastasis, which are the three most widely adopted combinatorial cancer therapies to improve the defects of PDT to optimize the treatment effect. Based on the above, an imaging-guided therapeutic nanoplatform integrating diagnosis and treatment has brought more optimized treatment effects to PDT. Finally, current challenges and prospects regarding these promising combinatorial cancer therapies are discussed. With a great deal of recent technological improvements, PDT is becoming a revolutionary development in the field of cancer medicine and the backbone of many emerging combination therapies. © 2022 Elsevier B.V.