AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

• Tác giả: Swapnil Subhash Bawage, M G Finn, Robert Hincapie, Gabriel A Kwong, Inho Lee, Zhonghan Li, Quoc D Mac, Hathaichanok Phuengkham, Peng Qiu, Hitha Rajesh, Leonard C Rogers, Aaron D Silva Trenkle, Anirudh Sivakumar, Sofia Vainikos, Min Xue
• Ngôn ngữ: eng
• Ký hiệu phân loại: 809.008 History and description with respect to kinds of persons
• Thông tin xuất bản: England : Nature nanotechnology , 2025
• Bộ sưu tập: NCBI
• ID: 720685

Tóm tắt

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