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Herein, we established a dual-trigger-mediated synergistic strategy to form a reticulated peptide network in situ by functional peptide (CL-YPFG) through responsive self-assembly and covalent labeling for prolonged imaging and boosted accumulation of drugs. Specifically, the CL-YPFG underwent morphology transformation from nanoparticles to nanofibers under alkaline phosphatase and further turned into reticulated peptide structures in the presence of nitroreductase by generating highly electrophilic quinone methide intermediates for covalent labeling of proximal peptides or proteins, enabling prolonged tumor retention. By replacing the functional groups on CL-YPFG, it could be readily endowed with imaging (organic dyes for fluorescence imaging and chelator moieties for 1H magnetic resonance imaging) and therapeutic (photodynamic therapy and immunotherapy) capabilities, demonstrating the versatility of peptide-based scaffolds for enhanced tumor-specific imaging\/therapy.<\/jats:p>","DOI":"10.1021\/jacs.6c08269","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:32:49Z","timestamp":1787653969000},"page":"36782-36793","source":"Crossref","is-referenced-by-count":0,"title":["<i>In Situ<\/i>\n                    Construction of a Reticulated\nPeptide Scaffold via Responsive Self-Assembly and Proximal Covalent\nLabeling for Enhanced Tumor Imaging and Therapy"],"prefix":"10.1021","volume":"148","author":[{"given":"Ruxin","family":"Feng","sequence":"first","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilu","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Ning","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumin","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingqing","family":"Feng","sequence":"additional","affiliation":[{"name":"China\u2013Japan Friendship Hospital , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-0040","authenticated-orcid":true,"given":"Suying","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-7764","authenticated-orcid":true,"given":"Leyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing University of Chemical Technology , , ,","place":["Beijing, China, 100029"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"issue":"23","key":"2026090312084421600_cit1","doi-asserted-by":"publisher","first-page":"12992","DOI":"10.1002\/anie.202102377","article-title":"High-Contrast Fluorescence Diagnosis\nof Cancer Cells\/Tissues Based on \u03b2-Lapachone-Triggered ROS Amplification\nSpecific in Cancer Cells","volume":"60","author":"Liu","year":"2021","journal-title":"Angew. 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