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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy
- Title
- Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy
- Authors
- Lee; Youngjoo; Song; Sukyung; Yang; Suah; Kim; Jinseong; Moon; Yujeong; Shim; Nayeon; Yoon; Hong Yeol; Sehoon; Man Kyu; Kwangmeyung
- Ewha Authors
- 김광명
- SCOPUS Author ID
- 김광명
- Issue Date
- 2024
- Journal Title
- Acta Pharmaceutica Sinica B
- ISSN
- 2211-3835
- Citation
- Acta Pharmaceutica Sinica B vol. 14, no. 3, pp. 1428 - 1440
- Keywords
- Anti-PD-L1 peptide; Cancer immunotherapy; Crosslinked lipid nanoparticles; Immune checkpoint blockade; Lysosomal PD-L1 degradation; PD-L1 multivalent binding; PEGylated liposome; Tumor-targeting
- Publisher
- Chinese Academy of Medical Sciences
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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
- DOI
- 10.1016/j.apsb.2023.09.007
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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