2025-01-13 ジョージア工科大学
<関連情報>
- https://research.gatech.edu/new-biosensors-could-revolutionize-cancer-detection
- https://www.nature.com/articles/s41565-024-01834-8
抗腫瘍免疫のプログラム可能な検出のためのANDゲートプロテアーゼ活性化ナノセンサー AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity
Anirudh Sivakumar,Hathaichanok Phuengkham,Hitha Rajesh,Quoc D. Mac,Leonard C. Rogers,Aaron D. Silva Trenkle,Swapnil Subhash Bawage,Robert Hincapie,Zhonghan Li,Sofia Vainikos,Inho Lee,Min Xue,Peng Qiu,M. G. Finn & Gabriel A. Kwong
Nature Nanotechnology Published:03 January 2025
DOI:https://doi.org/10.1038/s41565-024-01834-8
Abstract
The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides. These actuate by releasing a reporter if and only if cleaved by a specific pair of proteases. AND-gated nanosensors that detect the concomitant activity of the granzyme B protease secreted by CD8 T cells and matrix metalloproteinases overexpressed by cancer cells identify the unique condition of cytotoxic T cell killing of tumour cells. In preclinical mouse models, AND-gated nanosensors discriminate tumours that are responsive to immune checkpoint blockade therapy from B2m–/– tumours that are resistant to it, minimize signals from tissues without co-localized protease expression including the lungs during acute influenza infection, and release a reporter locally in tissue or distally in the urine for facile detection.
