PD1細胞膜被覆Ru(II)-Pt(IV)複合ナノ粒子によるカスケード免疫活性化を介した肝転移性黒色腫の阻害

Chemotherapy and photodynamic therapy (PDT) can indirectly increase T cell infiltration in metastatic melanoma by inducing immunogenic cell death (ICD) effects that activate the innate immune system. However, this indirect adaptive immune activation show limited efficacy in treating liver metastatic melanoma, mainly because the presence of abundant inimmunosuppressive cells within liver metastases leads to impaired function of the ICD-activated effector T cells. Therefore, to combine indirectly increased T cell infiltration with directly enhanced T cell killing function for initiating a cascaded immune process, we report herein an engineered PD1 cell membrane-coated Ru(ll)-Pt(lV) complex nanoparticle (Ru-Pt-Ru@PD1) for integrated chemo/PDT/ICB therapy. Ru-Pt-Ru@PD1 enhances the accumulation of Ru and Pt in tumors to induce the ICD effects and activate innate and adaptive immunity. Moreover, the engineered PD1 cell membrane continuously blocks the PD1/PDL1 immunosuppressive axis, a key advantage over common monoclonal antibodies that are rapidly captured by macrophage receptor. Ultimately, Ru-Pt-Ru@PD1 increases T cells infiltration and and restores the killing function of these T cells, enabling a cascaded and sustained immune response. Ru-Pt-Ru@PD1 significantly suppressed both proximal melanoma and distal liver cancer in a mouse model bearing melanoma and liver cancer simultaneously, and prevent primary and metastatic tumors with a high tumor inhibition rate (TIR) of 92.2% for the primary melanoma and significantly inhibited metastasis of melanoma in the liver and other organs, in a melanoma metastasis mouse model. Overall, this study provides an effective method for cascaded amplification of antitumor immune effects, demonstrating the clinical potential for metastatic melanoma treatment.