The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis.Photothermal therapy(PTT)triggers the release of tumor-specific antigens and damage associated molecular...The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis.Photothermal therapy(PTT)triggers the release of tumor-specific antigens and damage associated molecular patterns(DAMPs)in-situ.However,the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells.Therefore,systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect.To this end,polyethylene glycol(PEG)-stabilized platinum(Pt)nanoparticles(Pt NPs)conjugated with a PD-L1 inhibitor(BMS-1)through a thermo-sensitive linkage were constructed.Upon near-infrared(NIR)exposure,BMS-1 was released and maleimide(Mal)was exposed on the surface of Pt NPs,which captured the antigens released from the ablated tumor cells,resulting in the enhanced antigen internalization and presentation.In addition,the Pt NPs acted as immune adjuvants by stimulating dendritic cells(DCs)maturation.Furthermore,BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues.Thus,Pt NPs can ablate tumors through PTT,and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration,thereby preventing tumor relapse and metastasis.展开更多
基金The authors acknowledge the financial support from National Natural Science Foundation of China(Grant Nos.21975246 and 51903233)The project was supported by Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences.
文摘The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis.Photothermal therapy(PTT)triggers the release of tumor-specific antigens and damage associated molecular patterns(DAMPs)in-situ.However,the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells.Therefore,systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect.To this end,polyethylene glycol(PEG)-stabilized platinum(Pt)nanoparticles(Pt NPs)conjugated with a PD-L1 inhibitor(BMS-1)through a thermo-sensitive linkage were constructed.Upon near-infrared(NIR)exposure,BMS-1 was released and maleimide(Mal)was exposed on the surface of Pt NPs,which captured the antigens released from the ablated tumor cells,resulting in the enhanced antigen internalization and presentation.In addition,the Pt NPs acted as immune adjuvants by stimulating dendritic cells(DCs)maturation.Furthermore,BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues.Thus,Pt NPs can ablate tumors through PTT,and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration,thereby preventing tumor relapse and metastasis.
