Genetically Engineering Cell Membrane-Coated BTO Nanoparticles for MMP2-activated Piezocatalysis-immunotherapy.
Qingshuang TangSuhui SunPing WangLihong SunYuan WangLulu ZhangMenghong XuJing ChenRuiqi WuJinxia ZhangMing GongQingfeng ChenXiaolong LiangPublished in: Advanced materials (Deerfield Beach, Fla.) (2023)
Tumor immunotherapy based on immune checkpoint blockade (ICB) still suffers from low host response rate and non-specific distribution of immune checkpoint inhibitors, greatly compromising the therapeutic efficiency. Herein, cellular membrane stably expressing matrix metallopeptidase 2 (MMP2)-activated PD-L1 blockades was engineered to coat ultrasmall barium titanate (BTO) nanoparticle for overcoming the immunosuppressive microenvironment of tumors. The resulting M@BTO NPs can significantly promote the BTO's tumor accumulation, while the masking domains on membrane PD-L1 antibodies were cleaved when exposure to MMP2 highly expressed in tumor. With ultrasound irradiation, M@BTO NPs can simultaneously generate reactive oxygen species (ROS) and O 2 based on BTO mediated piezocatalysis and water splitting, significantly promoting the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and improving the PD-L1 blockade therapy to the tumor, resulting in effective tumor growth inhibition and lung metastasis suppression in a melanoma mouse model. This nanoplatform combined MMP2-activated genetic editing cell membrane with US responsive BTO for both immune stimulation and specific PD-L1 inhibition, providing a safe and robust strategy in enhancing immune response against tumor. This article is protected by copyright. All rights reserved.