{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:35:00Z","timestamp":1792773300910,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"59","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404685"],"award-info":[{"award-number":["82404685"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82575061"],"award-info":[{"award-number":["82575061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Targeted degradation of membrane proteins via the lysosomal pathway holds great therapeutic promise, yet existing platforms rely on bulky ligands such as glycopolymers, antibodies, or protein nanocages, which complicate synthesis and limit tissue penetration. Here, we repurpose L\u2011type amino acid transporter 1 (LAT1)\u2014a nutrient transporter overexpressed in diverse cancers\u2014as a lysosomal targeting receptor. Taking advantage of LAT1\u2018s natural substrate preference, we design a minimalist chemical handle: a single phenylalanine derivative that serves as a high\u2011affinity LAT1 ligand. This ligand is conjugated via bioorthogonal chemistry to various warheads (antibodies or small molecules) to generate modular degraders termed LAT1\u2010mediated lysosome\u2010targeting chimeras (LA\u2011LYTAC). These chimeras efficiently internalize and route oncogenic membrane proteins\u2014including PD\u2011L1, EGFR, and integrins\u2014to lysosomes for degradation. The platform operates through a LAT1\u2011dependent, lysosomal mechanism and suppresses downstream signaling pathways. In a syngeneic mouse model of triple\u2011negative breast cancer, a PD\u2011L1\u2011targeting LA\u2011LYTAC reduces tumor growth by more than 60%, enhances CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration, and shows no overt toxicity. This work establishes a synthetically accessible, truly modular, and tumor\u2011selective degradation platform driven by a single amino acid, offering a streamlined alternative to existing lysosome\u2011targeting technologies.\n                  <\/jats:p>","DOI":"10.1002\/advs.76862","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:21:07Z","timestamp":1785756067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Single\u2010Amino\u2010Acid Ligand for LAT1: A Minimalist and Modular Platform for Lysosome\u2010Targeted Degradation of Membrane Proteins"],"prefix":"10.1002","volume":"13","author":[{"given":"Liquan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3038-7800","authenticated-orcid":false,"given":"Haotian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5534-4837","authenticated-orcid":false,"given":"Hongchao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-8161","authenticated-orcid":false,"given":"Da","family":"Qian","sequence":"additional","affiliation":[{"name":"Central Laboratory, Department of Burn and Plastic Surgery\u2010Hand Surgery Changshu Hospital Affiliated to Soochow University Changshu No.1 People's Hospital Changshu Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-0232","authenticated-orcid":false,"given":"Xuli","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, Cancer Center Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer  Hangzhou Zhejiang 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Acid Transporter LAT1 Is Expressed on Cancer Cell\u2010Derived Exosomes with Potential as a Diagnostic and Prognostic Biomarker","volume":"14","author":"Liu Y. 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