Nanorobots Hold PD-L1 and Break Membrane of Colorectal Cancer Cells for Immunotherapy

Limited immune cell infiltration is the main reason for poor immunotherapy efficacy in colorectal cancer (CRC) patients. Herein, we design a peptide-based nanorobot (NRb) that recognizes PD-L1 and breaks cancer cell membranes by forming fibrils though a pH responsive module. NRb shows long retention in targeted tumours (>120 h) though interaction with PD-L1 and blocks PD-1/PD-L1 to activate T cell killing effect. At the same time, at the tumour microenvironment pH 6.5, it forms fibrils that break the cancer cell membrane, inducing immunogenic cell death (ICD) with the release of damage-associated molecular patterns (DAMPs) and the subsequent infiltration of T cells. NRb shows higher therapeutic efficacy than the regimen of alpha PD-L1+Oxaliplatin in a variety of CRC-tumor bearing mouse models and has good biocompatibility due to the targeted break of cancer cells, exhibiting great potential for CRC immunotherapy in clinic.