Nanorobots Enhance Immune Cell Recognition for Colorectal Cancer Therapy

Colorectal cancer, the abnormal growth of cancerous cells in the large intestine or the rectum, is one of the most common types of cancers worldwide. Available treatments for this type of cancer include chemotherapy, radiation therapy, surgery and interventions designed to strengthen patients' immune system (i.e., immunotherapies). Immunotherapy is designed to boost the body's immune system, via the use of drugs that increase the activity of immune cells and prompt them to target cancerous cells and prevent their growth. Despite its potential, immunotherapy is often ineffective, typically because not enough immune cells successfully enter and recognize tumors. Researchers at Xinqiao Hospital's Army Medical University, the CAS Center for Excellence in Nanoscience and other institutes in China recently developed a nanorobot that could help to overcome this limitation, recognizing cancerous cells and making it easier for immune cells to target them. The robot, introduced in a paper published in Nature Nanotechnology, also proved to be biocompatible in initial tests, suggesting that it could be safely deployed inside the human body. "Limited immune cell infiltration is the main reason for poor immunotherapeutic efficacy in colorectal cancer patients," wrote Wang Ying, Chuanhao Zheng and their colleagues wrote in their paper. "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." A tiny robot that responds to biological signals The new nanorobot developed by Ying, Zheng and their colleagues essentially consists of a carefully engineered peptide sequence (i.e., a set of short amino acid chains, which are the building blocks of proteins). The robot can recognize a protein called PD-L1, which is typically present in colorectal cancer cells. When it binds to this protein, the peptides block a pathway via which cancerous cells typically hide from immune cells (i.e., the PD-1/PD-L1 interaction). In response to the low pH in cancerous tissue, the nanorobot assembles into fiber-like structures that disrupt the membrane on abnormal cells, which attract T cells (i.e., white blood cells that play a key role in fighting both cancer and infections). "The nanorobot shows long retention in targeted tumors (>120 h) through interaction with PD-L1 and blocks PD-1/PD-L1 to activate the T cell killing effect," wrote the authors. "At the same time, in the tumor 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." A possible upgrade for future cancer treatments The researchers have so far tested their nanorobot in adult mice that had colorectal tumors, assessing its safety and its effectiveness compared to standard immunotherapy and chemotherapy interventions. Notably, their peptide-based system was found to outperform both these treatments, allowing more T-cells to infiltrate into tumors and prompting the death of more cancerous cells, causing less damage to healthy tissues. "The nanorobot shows higher therapeutic efficacy than the regimen of αPD-L1+oxaliplatin in a variety of colorectal-cancer-tumor-bearing mouse models and has good biocompatibility due to the targeted breakage of cancer cells, exhibiting great potential for colorectal cancer immunotherapy in clinic," wrote Ying, Zheng and their colleagues. In the future, the team's nanorobot could be improved and tested further, first in additional experiments and eventually in clinical trials. If the results of these trials are favorable, they could eventually open new opportunities for the treatment of colorectal cancer with carefully engineered nanotechnologies. © 2026 Science X Network