Thermosensitive Liposomes Activate STING Pathway For Photothermal Immunotherapy Of Lung Cancer

Immunotherapy has brought new hope for the treatment of lung cancer.However,due to the tumor immunosuppressive microenvironment and complex immune mechanisms,it is still difficult to develop effective and safe immunotherapy methods.Studies have shown that photothermal therapy can cause immunogenic tumor death,release tumor-associated antigens,improve immune cell infiltration,and improve tumor microenvironment.Moreover,N2-region photothermal therapy could induce deeper and more uniform immunogenic death within the tumor.In addition,c GAS-STING as an innate immune pathway has important positive significance for the treatment of tumors.Therefore,by combining photothermal therapy with c GAS-STING immunotherapy,the limitations of tumor microenvironment and complex immune mechanisms are overcome,and it is expected to play a highly effective photothermal immunotherapy combined with anti-lung cancer treatment.Based on the immunosuppressive microenvironment within the tumor,this study first induced immunogenic death of the tumor by photothermal therapy,released tumor-associated antigens and cytokines,and improved the infiltration of immune cells,thereby improving the tumor microenvironment.At the same time,photothermal sensitive liposomes can trigger the release of DMXAA under the action of808 nm light,activate the c GAS-STING signaling pathway,induce the apoptosis of tumor cells and promote the maturation of immune cells,so as to realize the precise photothermal immunotherapy against lung cancer under the guidance of near-infrared II region light.The thermosensitive liposomes loaded with photothermal agent DTTB and STING agonist DMXAA,named PLDD,were synthesized by nano-precipitation method.PLDD had good physical and chemical characteristics detected by transmission electron microscopy and Darwin particle size analyzer.The results of laser confocal and flow cytometry showed that it had a good combined anti-tumor effect in vitro.808 nm fluorescence imaging and photoacoustic imaging showed that the drug could reach the highest concentration in the tumor site at 12 hours after drug administration.The LLC subcutaneous tumor model of lung cancer was constructed in vivo.It was found that PLDD improved the tumor microenvironment by activating tumor immunogenic death under the action of 808 nm,and activated the c GAS-STING immune pathway to promote the maturation of immune cells through the DMXAA released,thus playing a highly efficient photothermal immune combined effect.