Nanorobots hold PD-L1 and break membrane of colorectal cancer cells for immunotherapy
Menée in vitro et à l'aide de modèles murins de cancer colorectal, cette étude met en évidence l'intérêt thérapeutique d'un nanorobot capable de reconnaître le ligand PD-L1 via un peptide et de casser les membranes des cellules cancéreuses en formant, à un certain pH, des fibrilles dans le microenvironnement tumoral
Limited immune cell infiltration is the main reason for poor immunotherapeutic efficacy in colorectal cancer patients. Here we design a peptide-based nanorobot that recognizes PD-L1 and breaks cancer cell membranes by in situ forming fibrils through a pH-responsive module. The nanorobot shows long retention in targeted tumours (>120 h) through interaction with PD-L1 and blocks PD-1/PD-L1 to activate the T cell killing effect. At the same time, in the tumour microenvironment (pH 6.5), it forms fibrils that break the cancer cell membrane, inducing immunogenic cell death with the release of damage-associated molecular patterns and the subsequent infiltration of T cells. The nanorobot shows higher therapeutic efficacy than the regimen of αPD-L1+oxaliplatin in a variety of colorectal-cancer-tumour-bearing mouse models and has good biocompatibility due to the targeted breakage of cancer cells, exhibiting great potential for colorectal cancer immunotherapy in clinic.
Nature Nanotechnology , article en libre accès, 2026