Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events.Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect.Herein,we designed a Gd-based metal-organic framework(Gd-MOF)nanosystem for MRI-guided thermotherapy and synergistic immunotherapy,which featured high performance in drug loading and tumor tissue penetration.The PD-1 inhibitor(aPD-1)was initially loaded in the porous Gd-MOF(Gd/M)nanosystem.Then,the phase change material(PCM)and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM(Gd/MPC).When entering the tumor microenvironment(TME),Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness,improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1.Meanwhile,Gd/MPC can be used for contrast-enhanced MRI.Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun,and ultimately leads to the apoptosis of cancer cells after treatment.In general,Gd/MPC nanosystem not only solves the problem of system side effect,but also achieves the controlled drug release via PCM,providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.