A new study in Nature Nanotechnology introduces a radically different approach to colorectal cancer immunotherapy: peptide-based nanorobots that simultaneously block immune checkpoint signaling and physically rupture cancer cell membranes—turning immunologically “cold” tumors into T-cell–inflamed targets.
Colorectal cancer (CRC) has long been resistant to immunotherapy, largely because most tumors exhibit poor immune cell infiltration and limited responsiveness to PD-1/PD-L1 blockade outside of MSI-H/dMMR subtypes. To overcome this barrier, researchers from Chongqing Medical University, the Chinese Academy of Sciences, and international collaborators engineered a PD-L1–targeting nanorobot (NRb) designed to remain localized within tumors, disrupt cancer cells directly, and activate systemic antitumor immunity.
The nanorobot is built from self-assembling peptides and incorporates two key functional modules. First, it selectively binds to PD-L1 on tumor cell membranes, enabling prolonged tumor retention (>120 hours) while simultaneously blocking the PD-1/PD-L1 immune checkpoint to restore T-cell activity. Second, it contains a pH-responsive module that exploits the acidic tumor microenvironment (pH ~6.5). Under these conditions, the nanorobot undergoes in situ fibrillogenesis—forming rigid nanofibers that physically disrupt cancer cell membranes, triggering cell death.