Immune amplifying hydrogel microspheres with STING activation improve tumor retention for photoimmunotherapy

Abstract

STING agonists have shown a great promise in tumor immunotherapy by activating innate immunity. However, systemic administration can easily lead to cytokine storm, and poor retention in tumor cannot activate a highly effective immune response. Herein, our photoimmune hydrogel microspheres directly addressed the above challenges. Immunonanoparticles were first synthesized by the hydrophilic interaction among polymer PEG-PCL, photosensitizer Cypate and STING agonist MSA-2. Then, the nanoparticles mixed with GelMA and photoinitiator were used as water phase, mineral oil was the oil phase. An immune amplifying hydrogel microsphere was finally constructed by regulating the flow ratio of water and oil phases through an injection pump and a microfluidic chip, which could improve the tumor retention of STING agonist to reverse the immunosuppressive microenvironment in tumors. The photothermal and photodynamic effect generated from the photosensitizer Cypate and the sustained release of STING agonist MSA-2 promoted the release of IFN-α and IFN-β by cGAS-STING pathway, which further strengthened the photoimmune activation. In vivo data demonstrated the tumor retention of hydrogel microspheres and enhanced the infiltration of T cells in tumor. Our work demonstrated an effective therapeutic strategy for innate immunotherapy in osteosarcoma, as well as an idea for other immunosuppressive tumors.