Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy

Abstract

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.

Alginate-Chitosan Biodegradable and Biocompatible Based Hydrogel for Breast Cancer Immunotherapy and Diagnosis: A Comprehensive Review

“…This bioresponsive gel may harness local ROS to facilitate immunotherapy drug release. Thereby improving combination therapy efficacy, modifying the TME, restraining tumor growth, inducing memory immunity, and protecting against tumor rechallenge . In this study, a novel approach for breast cancer treatment has been developed involving gefitinib-loaded cellulose acetate butyrate nanoparticles (Gnb-NPs) loaded in chitosan/β-glycerophosphate hydrogels.…”

“…Hence, as a result, it concluded that the prepared hydrogel could inhibit the growth of tumors in breast cancer. 192 Chen et al 193 developed an innovative immunotherapy approach utilizing injectable reactive oxygen species (ROS) within responsive hydrogels. These hydrogels sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a STING agonist, and indocyanine green (ICG) in response to the high ROS levels in the tumor microenvironment (TME).…”

“…Thereby improving combination therapy efficacy, modifying the TME, restraining tumor growth, inducing memory immunity, and protecting against tumor rechallenge. 193 In this study, a novel approach for breast cancer treatment has been developed involving gefitinib-loaded cellulose acetate butyrate nanoparticles (Gnb-NPs) loaded in chitosan/β-glycerophosphate hydrogels. The optimized Gnb-NPs were then incorporated into chitosan hydrogels by forming Gnb-NPs-hydrogel.…”