{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:52:10Z","timestamp":1792605130671,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Nanotechnol."],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1038\/s41565-024-01801-3","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T11:04:59Z","timestamp":1730113499000},"page":"296-302","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Targeted protein degradation via cellular trafficking of nanoparticles"],"prefix":"10.1038","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-4346","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2887-7545","authenticated-orcid":false,"given":"Runhan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-2177","authenticated-orcid":false,"given":"Xue","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0967-7556","authenticated-orcid":false,"given":"Haoying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4642-806X","authenticated-orcid":false,"given":"Linlin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2297-3053","authenticated-orcid":false,"given":"Mengke","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-1376","authenticated-orcid":false,"given":"Yan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-1062","authenticated-orcid":false,"given":"Meng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8133-4955","authenticated-orcid":false,"given":"Kam W.","family":"Leong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1043-3163","authenticated-orcid":false,"given":"Bingyang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"1801_CR1","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/s41573-019-0047-y","volume":"18","author":"M Schapira","year":"2019","unstructured":"Schapira, M., Calabrese, M. F., Bullock, A. N. & Crews, C. M. Targeted protein degradation: expanding the toolbox. Nat. Rev. Drug Discov. 18, 949\u2013963 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1801_CR2","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/s41589-019-0362-y","volume":"15","author":"PP Chamberlain","year":"2019","unstructured":"Chamberlain, P. P. & Hamann, L. G. Development of targeted protein degradation therapeutics. Nat. Chem. Biol. 15, 937\u2013944 (2019).","journal-title":"Nat. Chem. Biol."},{"key":"1801_CR3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41392-022-00966-4","volume":"7","author":"L Zhao","year":"2022","unstructured":"Zhao, L., Zhao, J., Zhong, K., Tong, A. & Jia, D. Targeted protein degradation: mechanisms, strategies and application. Signal Transduct. Target. Ther. 7, 113 (2022).","journal-title":"Signal Transduct. Target. Ther."},{"key":"1801_CR4","doi-asserted-by":"publisher","first-page":"e202100270","DOI":"10.1002\/cbic.202100270","volume":"23","author":"Z Hu","year":"2022","unstructured":"Hu, Z. & Crews, C. M. Recent developments in PROTAC-mediated protein degradation: from bench to clinic. ChemBioChem 23, e202100270 (2022).","journal-title":"ChemBioChem"},{"key":"1801_CR5","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.molcel.2019.09.009","volume":"76","author":"D Takahashi","year":"2019","unstructured":"Takahashi, D. et al. AUTACs: cargo-specific degraders using selective autophagy. Mol. Cell 76, 797\u2013810.e10 (2019).","journal-title":"Mol. Cell"},{"key":"1801_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28520-4","volume":"13","author":"CH Ji","year":"2022","unstructured":"Ji, C. H. et al. The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy\u2013lysosome system. Nat. Commun. 13, 904 (2022).","journal-title":"Nat. Commun."},{"key":"1801_CR7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41587-021-01173-2","volume":"40","author":"K Garber","year":"2022","unstructured":"Garber, K. The PROTAC gold rush. Nat. Biotechnol. 40, 12\u201316 (2022).","journal-title":"Nat. Biotechnol."},{"key":"1801_CR8","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41586-020-2545-9","volume":"584","author":"SM Banik","year":"2020","unstructured":"Banik, S. M. et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584, 291\u2013297 (2020).","journal-title":"Nature"},{"key":"1801_CR9","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41586-022-05235-6","volume":"610","author":"H Marei","year":"2022","unstructured":"Marei, H. et al. Antibody targeting of E3 ubiquitin ligases for receptor degradation. Nature 610, 182\u2013189 (2022).","journal-title":"Nature"},{"key":"1801_CR10","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.medj.2022.12.001","volume":"4","author":"P Zhang","year":"2023","unstructured":"Zhang, P. et al. Cancer nanomedicine toward clinical translation: obstacles, opportunities, and future prospects. Med 4, 147\u2013167 (2023).","journal-title":"Med"},{"key":"1801_CR11","doi-asserted-by":"publisher","first-page":"5397","DOI":"10.1039\/D0CS01127D","volume":"50","author":"M Sousa de Almeida","year":"2021","unstructured":"Sousa de Almeida, M. et al. Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine. Chem. Soc. Rev. 50, 5397\u20135434 (2021).","journal-title":"Chem. Soc. Rev."},{"key":"1801_CR12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.addr.2019.04.008","volume":"143","author":"ND Donahue","year":"2019","unstructured":"Donahue, N. D., Acar, H. & Wilhelm, S. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Adv. Drug Deliv. Rev. 143, 68\u201396 (2019).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"1801_CR13","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/j.drudis.2021.12.007","volume":"27","author":"L Gautam","year":"2022","unstructured":"Gautam, L. et al. Multicompartment systems: a putative carrier for combined drug delivery and targeting. Drug Discov. Today 27, 1184\u20131195 (2022).","journal-title":"Drug Discov. Today"},{"key":"1801_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s13238-016-0323-0","volume":"9","author":"K Tsuchikama","year":"2018","unstructured":"Tsuchikama, K. & An, Z. Antibody\u2013drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell 9, 33\u201346 (2018).","journal-title":"Protein Cell"},{"key":"1801_CR15","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s10555-017-9687-8","volume":"36","author":"MJ Xu","year":"2017","unstructured":"Xu, M. J., Johnson, D. E. & Grandis, J. R. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev. 36, 463\u2013473 (2017).","journal-title":"Cancer Metastasis Rev."},{"key":"1801_CR16","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1158\/1535-7163.MCT-15-0565","volume":"15","author":"I Kj\u00e6r","year":"2016","unstructured":"Kj\u00e6r, I. et al. Cetuximab resistance in squamous carcinomas of the upper aerodigestive tract is driven by receptor tyrosine kinase plasticity: potential for mAb mixtures. Mol. Cancer Ther. 15, 1614\u20131626 (2016).","journal-title":"Mol. Cancer Ther."},{"key":"1801_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0928-4","volume":"18","author":"X Jiang","year":"2019","unstructured":"Jiang, X. et al. Role of the tumor microenvironment in PD-L1\/PD-1-mediated tumor immune escape. Mol. Cancer 18, 10 (2019).","journal-title":"Mol. Cancer"},{"key":"1801_CR18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41571-019-0268-3","volume":"17","author":"D-Y Oh","year":"2020","unstructured":"Oh, D.-Y. & Bang, Y.-J. HER2-targeted therapies\u2014a role beyond breast cancer. Nat. Rev. Clin. Oncol. 17, 33\u201348 (2020).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1801_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","volume":"23","author":"CB Jackson","year":"2022","unstructured":"Jackson, C. B., Farzan, M., Chen, B. & Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell Biol. 23, 3\u201320 (2022).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1801_CR20","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41392-021-00740-y","volume":"6","author":"Y Chen","year":"2021","unstructured":"Chen, Y. et al. ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker. Signal Transduct. Target. Ther. 6, 315 (2021).","journal-title":"Signal Transduct. Target. Ther."},{"key":"1801_CR21","doi-asserted-by":"publisher","first-page":"923","DOI":"10.4049\/jimmunol.2001062","volume":"206","author":"CKV Devarakonda","year":"2021","unstructured":"Devarakonda, C. K. V., Meredith, E., Ghosh, M. & Shapiro, L. H. Coronavirus receptors as immune modulators. J. Immunol. 206, 923\u2013929 (2021).","journal-title":"J. Immunol."},{"key":"1801_CR22","doi-asserted-by":"publisher","first-page":"16982","DOI":"10.1021\/acsnano.1c04996","volume":"15","author":"R Tenchov","year":"2021","unstructured":"Tenchov, R., Bird, R., Curtze, A. E. & Zhou, Q. Lipid nanoparticles\u2014from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano 15, 16982\u201317015 (2021).","journal-title":"ACS Nano"},{"key":"1801_CR23","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.nantod.2011.02.003","volume":"6","author":"T-G Iversen","year":"2011","unstructured":"Iversen, T.-G., Skotland, T. & Sandvig, K. Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today 6, 176\u2013185 (2011).","journal-title":"Nano Today"},{"key":"1801_CR24","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/s41589-021-00770-1","volume":"17","author":"G Ahn","year":"2021","unstructured":"Ahn, G. et al. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat. Chem. Biol. 17, 937\u2013946 (2021).","journal-title":"Nat. Chem. Biol."},{"key":"1801_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22111-5","volume":"12","author":"R Wang","year":"2021","unstructured":"Wang, R. et al. Molecular basis of V-ATPase inhibition by bafilomycin A1. Nat. Commun. 12, 1782 (2021).","journal-title":"Nat. Commun."},{"key":"1801_CR26","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/s41580-021-00392-4","volume":"22","author":"YG Zhao","year":"2021","unstructured":"Zhao, Y. G., Codogno, P. & Zhang, H. Machinery, regulation and pathophysiological implications of autophagosome maturation. Nat. Rev. Mol. Cell Biol. 22, 733\u2013750 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1801_CR27","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1056\/NEJMoa1915722","volume":"384","author":"JJ Collier","year":"2021","unstructured":"Collier, J. J. et al. Developmental consequences of defective ATG7-mediated autophagy in humans. N. Engl. J. Med. 384, 2406\u20132417 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1801_CR28","doi-asserted-by":"publisher","first-page":"1804827","DOI":"10.1002\/adma.201804827","volume":"31","author":"W Wang","year":"2019","unstructured":"Wang, W. & Hu, Z. Targeting peptide-based probes for molecular imaging and diagnosis. Adv. Mater. 31, 1804827 (2019).","journal-title":"Adv. Mater."},{"key":"1801_CR29","doi-asserted-by":"publisher","first-page":"15532","DOI":"10.1074\/jbc.M212934200","volume":"278","author":"L Huang","year":"2003","unstructured":"Huang, L. et al. Novel peptide inhibitors of angiotensin-converting enzyme 2. J. Biol. Chem. 278, 15532\u201315540 (2003).","journal-title":"J. Biol. Chem."},{"key":"1801_CR30","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/ncb2082","volume":"12","author":"C Gao","year":"2010","unstructured":"Gao, C. et al. Autophagy negatively regulates Wnt signalling by promoting dishevelled degradation. Nat. Cell Biol. 12, 781\u2013790 (2010).","journal-title":"Nat. Cell Biol."},{"key":"1801_CR31","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/s41551-018-0284-0","volume":"2","author":"MA Islam","year":"2018","unstructured":"Islam, M. A. et al. Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA. Nat. Biomed. Eng. 2, 850\u2013864 (2018).","journal-title":"Nat. Biomed. Eng."},{"key":"1801_CR32","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/BF00300234","volume":"24","author":"MM Tomayko","year":"1989","unstructured":"Tomayko, M. M. & Reynolds, C. P. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother. Pharmacol. 24, 148\u2013154 (1989).","journal-title":"Cancer Chemother. Pharmacol."}],"container-title":["Nature Nanotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41565-024-01801-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41565-024-01801-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41565-024-01801-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T18:25:24Z","timestamp":1739903124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41565-024-01801-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,28]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["1801"],"URL":"https:\/\/doi.org\/10.1038\/s41565-024-01801-3","relation":{},"ISSN":["1748-3387","1748-3395"],"issn-type":[{"value":"1748-3387","type":"print"},{"value":"1748-3395","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,28]]},"assertion":[{"value":"10 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: B.S., M.Z., Y.L. and R.L. filed two patent applications based on this study to the State Intellectual Property Office of China and applied the Patent Cooperation Treaty. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}