Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 김광명 | - |
dc.date.accessioned | 2024-05-17T16:31:11Z | - |
dc.date.available | 2024-05-17T16:31:11Z | - |
dc.date.issued | 2024 | - |
dc.identifier.issn | 2211-3835 | - |
dc.identifier.other | OAK-35072 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/268284 | - |
dc.description.abstract | Immune checkpoint blockade (ICB) therapy targeting PD-L1 via monoclonal antibody (mAb) has shown extensive clinical benefits in the diverse types of advanced malignancies. However, most patients are completely refractory to ICB therapy owing to the PD-L1 recycling mechanism. Herein, we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes (immune checkpoint blockade liposomes; ICB-LPs) to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor cells. The ICB-LPs are prepared by formulation of DC8,9PC with photo-polymerized diacetylenic moiety, 1,2-dipalmitoylphosphatidylcholine (DPPC) and anti-PD-L1 peptide (D-form NYSKPTDRQYHF)-conjugated DSPE-PEG2k (anti-PD-L1-DSPE-PEG2k) in a molar ratio of 45:45:10, followed by cross-linking of liposomal bilayer upon UV irradiation. The 10 mol% anti-PD-L1-DSPE-PEG2k incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7 ± 1.04 nm, showing a high stability in serum condition. Importantly, the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane, which are endocytosed with aim to deliver PD-L1 to the lysosomes, wherein the durable PD-L1 degradation is observed for 72 h, in contrast to anti PD-L1 mAbs showing the rapid PD-L1 recycling within 9 h. The in vitro co-culture experiments with CD8+ T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 axis. When ICB-LPs are intravenously injected into colon tumor-bearing mice, they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting, inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 degradation. Collectively, this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward the lysosomes instead of the recycling endosomes. © 2024 The Authors | - |
dc.language | English | - |
dc.publisher | Chinese Academy of Medical Sciences | - |
dc.subject | Anti-PD-L1 peptide | - |
dc.subject | Cancer immunotherapy | - |
dc.subject | Crosslinked lipid nanoparticles | - |
dc.subject | Immune checkpoint blockade | - |
dc.subject | Lysosomal PD-L1 degradation | - |
dc.subject | PD-L1 multivalent binding | - |
dc.subject | PEGylated liposome | - |
dc.subject | Tumor-targeting | - |
dc.title | Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy | - |
dc.type | Article | - |
dc.relation.issue | 3 | - |
dc.relation.volume | 14 | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 1428 | - |
dc.relation.lastpage | 1440 | - |
dc.relation.journaltitle | Acta Pharmaceutica Sinica B | - |
dc.identifier.doi | 10.1016/j.apsb.2023.09.007 | - |
dc.identifier.wosid | WOS:001203194000001 | - |
dc.identifier.scopusid | 2-s2.0-85175608478 | - |
dc.author.google | Lee | - |
dc.author.google | Youngjoo | - |
dc.author.google | Song | - |
dc.author.google | Sukyung | - |
dc.author.google | Yang | - |
dc.author.google | Suah | - |
dc.author.google | Kim | - |
dc.author.google | Jinseong | - |
dc.author.google | Moon | - |
dc.author.google | Yujeong | - |
dc.author.google | Shim | - |
dc.author.google | Nayeon | - |
dc.author.google | Yoon | - |
dc.author.google | Hong Yeol | - |
dc.author.google | Sehoon | - |
dc.author.google | Man Kyu | - |
dc.author.google | Kwangmeyung | - |
dc.contributor.scopusid | 김광명(34770853900) | - |
dc.date.modifydate | 20240517125811 | - |