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dc.contributor.authorMoon, Yujeong-
dc.contributor.authorCho, Hanhee-
dc.contributor.authorKim, Jinseong-
dc.contributor.authorSong, Sukyung-
dc.contributor.authorPark, Jung Yeon-
dc.contributor.authorJin, Young Min-
dc.contributor.authorHan, Hee Eun-
dc.contributor.authorKim, Yongju-
dc.contributor.authorSeong, Joon­-Kyung-
dc.contributor.authorShim, Man Kyu-
dc.contributor.authorKim, Kwangmeyung-
dc.date.accessioned2024-12-20T12:00:31Z-
dc.date.available2024-12-20T12:00:31Z-
dc.date.created2024-12-18-
dc.date.issued2024-11-
dc.identifier.issn1433-7851-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/151382-
dc.description.abstractProteolysis-targeting chimeras (PROTACs) are a promising technique for the specific and durable degradation of cancer-related proteins via the ubiquitin-proteasome system in cancer treatment. However, the therapeutic efficacy of PROTACs is restricted due to their hydrophobicity, poor cell permeability and insufficient tumor-targeting ability. Herein, we develop the self-assembled peptide-derived PROTAC nanoparticles (PT-NPs) for precise and durable programmed death-ligand 1 (PD?L1) degradation in targeted tumors. The PT-NPs with an average size of 211.8?nm are formed through the self-assembly of amphiphilic peptide-derived PROTAC (CLQKTPKQC-FF-ALAPYIP), comprising a PD?L1-targeting ‘CLQKTPKQC’, self-assembling linker ‘FF’ and E3 ligase recruiting ‘ALAPYIP’. Particularly, PT-NPs strongly bind to tumor cell surface PD?L1 to form PD?L1/PT-NPs complex, then internalized through receptor-mediated endocytosis and degraded in lysosomes. Second, free PROTACs released from PT-NPs to the cytoplasm further induce the durable proteolysis of cytoplasmic PD?L1 via the ubiquitin-proteasome system. In colon tumor models, intravenously injected PT-NPs accumulate significantly at targeted tumor tissues through nanoparticle-derived passive and active targeting. At the targeted tumor tissues, PT-NPs promote durable PD?L1 degradation and ultimately trigger a substantial antitumor immune response. Collectively, this study provides valuable insights into the rational design of self-assembled peptide-derived PROTAC nanoparticles to ensure noticeable accuracy and enhanced efficacy in cancer treatment.-
dc.languageEnglish-
dc.publisherJohn Wiley & Sons Ltd.-
dc.titleSelf-Assembled Peptide-Derived Proteolysis-Targeting Chimera (PROTAC) Nanoparticles for Tumor-Targeted and Durable PD-L1 Degradation in Cancer Immunotherapy-
dc.typeArticle-
dc.identifier.doi10.1002/anie.202414146-
dc.description.journalClass1-
dc.identifier.bibliographicCitationAngewandte Chemie International Edition-
dc.citation.titleAngewandte Chemie International Edition-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
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KIST Article > 2024
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