Recent Progress in Photothermal, Photodynamic and Sonodynamic Cancer Therapy: Through the cGAS-STING Pathway to Efficacy-Enhancing Strategies

Abstract

Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer.

Keywords: cGAS-STING; cancer therapy; immunotherapy; photodynamic therapy; photothermal therapy; sonodynamic therapy; synergistic therapy.

Figure 1

The principles and results of two synergistic therapies of photothermal therapy and STING agonist and their effect on tumor in vivo. (A) Schematic illustration of a synergistic therapy of the photothermal transduction agent Indocyanine green (ICG) with the STING agonist DMXAA [30]. (B) Temperature development after the injection of ICG of different forms in vivo, the color represents different temperature, and have been shown in the legend [30]. (C) Tumor growth in vivo after photothermal therapy and a STING agonist alone and synergistic therapy. * p < 0.05 vs. control, *** p < 0.001 vs. control [30]. Copyright 2023 American Chemical Society. (D) Schematic illustration of a synergistic therapy of the photothermal transduction agent croconaine dye with the STING agonist diABZIs using SAPTNs [60]. (E) The images of drug distribution in vivo after the injection of SAPTNs with irradiation alone or with irradiation and the myeloperoxidase inhibitor PF1355, the color represents different temperature and the connection can be seen in the legend [60]. (F) Average volume of tumor reinjected in vivo after no treatment in the untreated group and SAPTNs plus PTT group treated by a synergistic therapy of PTT and a STING agonist using SAPTNs. *** p < 0.001 vs. control [60]. Copyright 2024 John Wiley and Sons.

Figure 2

The principle and result of two synergistic therapies of photodynamic therapy and STING agonist on primary tumors and distant tumors in vivo. (A) Schematic illustration of a synergistic therapy of the photosensitizer Meso-tetra(carboxyphenyl) porphyrin (TCPP) and STING agonist SR-717 [96]. Volume growth of a primary tumor (B) and distant tumor (C) when treated with a photodynamic material polymeric metal−organic framework (PMOF) and SR-717 alone and a synergistic therapy of PDT and a STING agonist by using a nanoparticles called SR@PMOF combining PMOF and a STING agonist (SR-717), without light irradiation (-L) or with light irradiation (+L). ** p < 0.01 vs. control, *** p < 0.001 vs. control [96]. Copyright 2023 American Chemical Society. (D) Schematic illustration of a synergistic therapy of a nanoparticle named GM@P, consisting of a hydrophobic shell encapsulating the photosensitizer MHI148 and the STING agonist 2′3′-cGAMP [31]. Tumor growth of primary tumors (E) and distant tumors (F) after photothermal therapy using a nanoparticle with MHI148 (M@P) alone without irradiation (Group B: M@P), with irradiation (Group D: M@P + light irradiation), with a free STING agonist and irradiation (group E: M@P + light irradiation + 2′3′-cGAMP), a STING agonist alone (Group C: 2′3′-cGAMP), and a synergistic therapy of GM@P (Group F: GM@P + light irradiation) and a control group (Group A). * p < 0.05 vs. control, ** p < 0.01 vs. control [31]. Copyright 2024 American Chemical Society.

Figure 3

The principle of a synergistic therapy of sonodynamic therapy and a cGAS-STING agonist using a material consisting of triphenyl phosphonium (TPP) and sonodynamic cobalt organic frame-work nanosheets (TPP@CoTCPP) and some experimental results. (A) Graphic illustration of TPP@CoTCPP [111]. (B) Comparison of the volume of ipsilateral and contralateral tumor in vivo in different groups treated by sonodynamic therapy and a STING agonist alone and a synergistic therapy of sonodynamic therapy and a cGAS-STING agonist. ns indicates not significant, ** p < 0.01 vs. control [111]. (C) Tumor volume of sonodynamic therapy alone and synergistic therapy [111]. Copyright 2023 Elsevier.