Targeted Nanophotoimmunotherapy Potentiates Cancer Treatment by Enhancing Tumor Immunogenicity and Improving the Immunosuppressive Tumor Microenvironment

Abstract

Cancer immunotherapy, such as immune checkpoint blockade, chimeric antigen receptor, and cytokine therapy, has emerged as a robust therapeutic strategy activating the host immune system to inhibit primary and metastatic lesions. However, low tumor immunogenicity (LTI) and immunosuppressive tumor microenvironment (ITM) severely compromise the killing effect of immune cells on tumor cells, which fail to evoke a strong and effective immune response. As an exogenous stimulation therapy, phototherapy can induce immunogenic cell death (ICD), enhancing the therapeutic effect of tumor immunotherapy. However, the lack of tumor targeting and the occurrence of immune escape significantly reduce its efficacy in vivo, thus limiting its clinical application. Nanophotoimmunotherapy (nano-PIT) is a precision-targeted tumor treatment that co-loaded phototherapeutic agents and various immunotherapeutic agents by specifically targeted nanoparticles (NPs) to improve the effectiveness of phototherapy, reduce its phototoxicity, enhance tumor immunogenicity, and reverse the ITM. This review will focus on the theme of nano-PIT, introduce the current research status of nano-PIT on converting “cold” tumors to “hot” tumors to improve immune efficacy according to the classification of immunotherapy targets, and discuss the challenges, opportunities, and prospects.

Porphyrins in Photodynamic Therapy: A Review

“…Therefore, to enhance PDT's efficacy, there is a need to strengthen ICD with synergistic tumour therapies. 308,[310][311][312][313][314] IPDT has emerged as a promising strategy, leveraging PDT to stimulate the immune response and combining it with immunotherapy. 304, 310-311, 313, 315-316 This approach aims to transform immune-OFF tumours into immune-ON ones, fostering a systemic immune response and preventing cancer recurrence.…”

Proton-Gradient-Driven Porphyrin-Based Liposome Remote-Loaded with Imiquimod as In Situ Nanoadjuvants for Synergistically Augmented Tumor Photoimmunotherapy

“…As reported, amphipathic, weakly acidic, and basic drugs could be loaded into the aqueous phase of liposomes with a high encapsulation efficiency (EE) and drug loading via the utilization of a difference in proton concentration across the membrane of liposomes. , Hence, for R837, a weakly basic drug, the liposome constructed by the transmembrane pH gradient loading method may achieve a high EE and endosomal membrane targeting. Besides, according to previous work, photodynamic therapy (PDT) could trigger immunogenic cell death (ICD) and tumor-associated antigen release and reverse “cold” tumors to “hot” tumors to improve tumor immunotherapy when combined with adjuvants. − Therefore, the combination of R837 and PDT may confer a synergistic and excellent therapeutic effect.…”

Recent Advances in Nanoimmunotherapy by Modulating Tumor-Associated Macrophages for Cancer Therapy

“…On the other hand, CAR-T therapy involves the genetic modification of the patient’s T cells in vitro, empowering them to recognize and target specific tumor antigens, thus leading to the effective destruction of tumor cells . Nonetheless, these therapies face substantial challenges when confronting solid tumors, primarily attributed to the immunosuppressive nature of the tumor microenvironment (TME) . The TME impedes T cell infiltration and antitumor effects, underscoring the significant importance of regulating the immunosuppressive TME in the context of cancer immunotherapy …”

“…6 Nonetheless, these therapies face substantial challenges when confronting solid tumors, primarily attributed to the immunosuppressive nature of the tumor microenvironment (TME). 7 The TME impedes T cell infiltration and antitumor effects, underscoring the significant importance of regulating the immunosuppressive TME in the context of cancer immunotherapy. 8 The TME encompasses a diverse array of components, including tumor cells, tumor-associated macrophages (TAMs), surrounding blood vessels, immune cells, fibroblasts, various signaling molecules, and the extracellular matrix.…”