Recent Advances in Reprogramming Strategy of Tumor Microenvironment for Rejuvenating Photosensitizers‐Mediated Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) has recently been considered a potential tumor therapy due to its time‐space specificity and non‐invasive advantages. PDT can not only directly kill tumor cells by using cytotoxic reactive oxygen species but also induce an anti‐tumor immune response by causing immunogenic cell death of tumor cells. Although it exhibits a promising prospect in treating tumors, there are still many problems to be solved in its practical application. Tumor hypoxia and immunosuppressive microenvironment seriously affect the efficacy of PDT. The hypoxic and immunosuppressive microenvironment is mainly due to the abnormal vascular matrix around the tumor, its abnormal metabolism, and the influence of various immunosuppressive‐related cells and their expressed molecules. Thus, reprogramming the tumor microenvironment (TME) is of great significance for rejuvenating PDT. This article reviews the latest strategies for rejuvenating PDT, from regulating tumor vascular matrix, interfering with tumor cell metabolism, and reprogramming immunosuppressive related cells and factors to reverse tumor hypoxia and immunosuppressive microenvironment. These strategies provide valuable information for a better understanding of the significance of TME in PDT and also guide the development of the next‐generation multifunctional nanoplatforms for PDT.

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy

“…This unique mechanism overcomes the issues of hypoxia and the limited depth of penetration of light in PDT. 86 Although CDT as a widely used ROS-mediated therapeutic strategy holds promise for cancer treatment, there are still several challenges that need to be addressed. Generally, an effective Fenton reaction requires a strong acidic environment (pH = 3−4), while the pH value of tumor tissues is approximately 6.5, resulting in a lower efficiency of CDT.…”

“…It is well-known that CDT relies on the reaction of H 2 O 2 with Fenton/Fenton-like catalysts to generate ·OH, without the need for O 2 or external energy input. This unique mechanism overcomes the issues of hypoxia and the limited depth of penetration of light in PDT . Although CDT as a widely used ROS-mediated therapeutic strategy holds promise for cancer treatment, there are still several challenges that need to be addressed.…”

Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy

“…Much of PDT-related research is focused on the development of novel agents for improved tumor specificity. − This can be achieved through two approaches. First, the modification of photosensitizers with biological conjugates, such as peptide or antibody conjugates, facilitates targeted delivery specifically to tumors .…”

Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot

“…This increases the efficacy of immunotherapy ( Wang-Bishop et al, 2020 ) in patients who had minimal benefited from initial clinical treatment. Importantly, extensive studies have shown that traditional therapies, such as chemotherapy ( Fabian et al, 2021 ; Kodumudi et al, 2010 ), targeted therapy, radiotherapy (RT) ( Huang et al, 2021 ; Vaes et al, 2021 ), and photodynamic therapy (PDT) ( Yu et al, 2023 ) can function as ICD inducers to activate the host-reactive immune response ( Rodriguez-Ruiz et al, 2020 ; Zhu et al, 2021 ), although they were originally acknowledged to directly kill tumor cells ( Cherniavsky et al, 2015 ). Notably, only a limited number of these traditional regimens serve as ICD inducers or induce sufficient ICD ( Fu et al, 2021 ).…”