{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:34:34Z","timestamp":1790886874325,"version":"4.1.0"},"reference-count":128,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009529","name":"COMSATS Institute of Information Technology","doi-asserted-by":"publisher","award":["CRGP 1628\/CRGP\/CUI\/LHR\/24"],"award-info":[{"award-number":["CRGP 1628\/CRGP\/CUI\/LHR\/24"]}],"id":[{"id":"10.13039\/100009529","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001688","name":"International Centre for Genetic Engineering and Biotechnology","doi-asserted-by":"publisher","award":["CRP\/PAK24-04_EC"],"award-info":[{"award-number":["CRP\/PAK24-04_EC"]}],"id":[{"id":"10.13039\/501100001688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2412035"],"award-info":[{"award-number":["W2412035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Targeted protein degradation (TPD) has revolutionized the therapeutic landscape of cancer therapy. TPD aids in avoiding cellular malfunction by recruiting the protein of interest (POI) into intracellular degradation machinery. The proteolysis-targeting chimeras (PROTACs) degradation hijacks the protein\u2019s disposal system and co-opts ubiquitin E3 ligase to degrade disease-associated proteins. Numerous PROTACs have come to the forefront in cancer therapy, and several are in clinical trials. PROTACs are on the verge of U.S. Food and Drug Administration (FDA) approval. However, the low bioavailability, inadequate delivery, non-specific biodistribution, and systemic toxicity are impairing their clinical potential. Nano-PROTACs have implications for precisely targeting intractable proteins. This review provides insights into the realm of cellular mechanisms of nano-PROTACs, especially for targeting bromodomain-containing protein 4 (BRD4), programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and indoleamine 2,3-dioxygenase (IDO). How stimuli-responsive linkages are introduced in polymeric nanoparticles to aid the controlled release of PROTACs is discussed. We provide a glimpse of how advanced polymer- and peptide-based nano-PROTACs degradation is being combined with photoimmunotherapy, radiation therapy, and chemotherapy to broaden the impact of cancer therapy. Opportunities and challenges of current strategies are discussed to preclude major limitations in clinical translation. The integration of nano-PROTACs with potentially curative therapeutic modalities may broaden the clinical performance of PROTACs.<\/jats:p>","DOI":"10.1021\/polymscitech.5c00122","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T16:47:59Z","timestamp":1775666879000},"page":"442-461","source":"Crossref","is-referenced-by-count":5,"title":["Engineering\nPolymeric Nano-PROTAC for Targeted Protein\nDegradation and Cancer Therapy"],"prefix":"10.1021","volume":"2","author":[{"given":"Madiha","family":"Saeed","sequence":"first","affiliation":[{"name":"COMSATS University Islamabad Lahore Campus , , ,","place":["Lahore, Pakistan, 54000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Amina","sequence":"additional","affiliation":[{"name":"COMSATS University Islamabad Lahore Campus , , ,","place":["Lahore, Pakistan, 54000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4391-2507","authenticated-orcid":true,"given":"Zhiai","family":"Xu","sequence":"additional","affiliation":[{"name":"East China Normal University , , ,","place":["Shanghai, China, 200241"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3398-0880","authenticated-orcid":true,"given":"Haijun","family":"Yu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"issue":"2","key":"2026072818070368900_cit1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41418-020-00703-w","article-title":"The Ubiquitin\nSystem: From Cell Signalling to Disease Biology and New Therapeutic\nOpportunities","volume":"28","author":"Damgaard","year":"2021","journal-title":"Cell Death Differ."},{"issue":"4","key":"2026072818070368900_cit2","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1021\/acs.chemrev.4c00595","article-title":"Protein-Based\nDegraders: From Chemical Biology Tools to Neo-Therapeutics","volume":"125","author":"Ou","year":"2025","journal-title":"Chem. Rev."},{"issue":"9","key":"2026072818070368900_cit3","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/s41580-024-00729-9","article-title":"Targeted Protein\nDegradation: From Mechanisms to Clinic","volume":"25","author":"Tsai","year":"2024","journal-title":"Nat.\nRev. Mol. Cell Biol."},{"issue":"3","key":"2026072818070368900_cit4","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC Targeted\nProtein Degraders:\nThe Past Is Prologue","volume":"21","author":"Be\u0301ke\u0301s","year":"2022","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"13","key":"2026072818070368900_cit5","doi-asserted-by":"publisher","first-page":"5330","DOI":"10.1039\/D1CS00762A","article-title":"Proteolysis-Targeting\nChimera (PROTAC) Delivery System: Advancing\nProtein Degraders towards Clinical Translation","volume":"51","author":"Chen","year":"2022","journal-title":"Chem. Soc. Rev."},{"issue":"1","key":"2026072818070368900_cit6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41392-022-00966-4","article-title":"Targeted Protein\nDegradation: Mechanisms, Strategies and Application","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"issue":"1","key":"2026072818070368900_cit7","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12943-021-01434-3","article-title":"Proteolysis-Targeting\nChimeras (PROTACs) in Cancer Therapy","volume":"21","author":"Li","year":"2022","journal-title":"Mol. Cancer"},{"issue":"1","key":"2026072818070368900_cit8","doi-asserted-by":"publisher","first-page":"6509","DOI":"10.1038\/s41467-023-42233-2","article-title":"Expanding PROTACtable Genome Universe\nof E3 Ligases","volume":"14","author":"Liu","year":"2023","journal-title":"Nat. Commun."},{"issue":"1","key":"2026072818070368900_cit9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41392-022-00966-4","article-title":"Targeted Protein\nDegradation: Mechanisms, Strategies and Application","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"issue":"1","key":"2026072818070368900_cit10","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41392-024-02004-x","article-title":"Targeted Protein Degradation:\nAdvances in Drug Discovery and Clinical Practice","volume":"9","author":"Zhong","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"2026072818070368900_cit11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.semcancer.2020.03.007","article-title":"Targeting the E3 Ubiquitin Ligases\nDCAF15 and Cereblon\nfor Cancer Therapy","volume":"67","author":"Nguyen","year":"2020","journal-title":"Target. 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A Phase 1, Multi-Center,\nOpen-Label, Dose Finding Study to Evaluate the Safety, Tolerability,\nPharmacokinetics, and Pharmacodynamics of Cc-94676 in Subjects With\nMetastatic Castration-Resistant Prostate Cancer; Clinical trial registration\nNCT04428788; clinicaltrials.gov,, 2024https:\/\/clinicaltrials.gov\/study\/NCT04428788 (accessed 2025-07-21)."},{"key":"2026072818070368900_cit127","unstructured":"A Phase 1, Dose Escalation\nand Cohort Expansion Study to Evaluate\nthe Safety, Pharmacokinetics and Clinical Activity of DT2216, an Antiapoptotic\nProtein Targeted Degradation Compound, in Patients With Relapsed\/Refractory\nMalignancies,, 2021https:\/\/clinicaltrials.gov\/study\/NCT04886622 (accessed 2021-08-25)."},{"key":"2026072818070368900_cit128","unstructured":"DT2216 in Combination\nWith Irinotecan for Children, Adolescents and\nYoung Adults With Relapsed or Refractory Solid Tumors: A Phase I Study\nWith Phase II Feasibility Cohort for Fibrolamellar Carcinoma, 2024https:\/\/clinicaltrials.gov\/study\/NCT06620302(accessed 2025-06-12)."}],"container-title":["Polymer Science &amp; Technology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/polymscitech.5c00122","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/pstoco\/article-pdf\/2\/7\/442\/66308638\/polymscitech.5c00122.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/pstoco\/article-pdf\/2\/7\/442\/66308638\/polymscitech.5c00122.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:09:28Z","timestamp":1785276568000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/pstoco\/article\/2\/7\/442\/5235535\/Engineering-Polymeric-Nano-PROTAC-for-Targeted"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":128,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4,8]]},"published-print":{"date-parts":[[2026,7,28]]}},"URL":"https:\/\/doi.org\/10.1021\/polymscitech.5c00122","relation":{},"ISSN":["2997-3279"],"issn-type":[{"value":"2997-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]}}}