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Transformable peptide nanoparticles inhibit the migration of N-cadherin overexpressed cancer cells
Institution:1. Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education & Hubei Key Laboratory of Catalysis and Materials Science, South-Central University for Nationalities, Wuhan 430074, China;2. CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China;1. School of Material Science and Engineering, Beijing Institute of Technology, Beijing 100081, China;2. CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), University of Chinese Academy of Sciences, Beijing 100190, China;1. School of Chemistry, Northeast Normal University, Changchun 130024, China;2. CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China;1. Key Laboratory of Functional Polymer Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China;2. School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, Tianjin 300070, China;3. CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China
Abstract:About 90% cancer-related mortality results from the cancer metastasis, which generally undergoes after epithelial-mesenchymal transition (EMT) process. N-Cadherin, overexpressed on cancer cell surface during EMT, can enhance the migration of cancer cells. Herein, we design and synthesize a transformable peptide BP-KLVFF-SWTLYTPSGQSK (BFS) that can block N-cadherin for inhibiting cancer migration and metastasis. The peptide BFS consists of three modules including (1) the hydrophobic bis-pyrene (BP) unit for forming and locating nanoparticles, (2) the KLVFF peptide sequence for forming and stabilizing fibrous structures and (3) the targeting peptide sequence SWTLYTPSGQSK that can specifically bind to N-cadherin. The peptide BFS can form nanoparticles in PBS, which can transform to nanofibers when targeting and binding to N-cadherin. The nanofibers inhibit the migration of N-cadherin overexpressed MDA-MB-436 cancer cells. The peptide BFS shows 83.6% inhibiting rate in cells wound healing assay. In addition, the inhibition rate is 67.9% when the BFS applied in transwell migration assay. These results indicate that the BFS has excellent ability to inhibit migration of cancer cells. This self-assembly strategy could be potentially utilized to regulate the key protein during EMT for inhibiting the tumor metastasis.
Keywords:Self-assembly  Peptide  N-Cadherin  Cancer  Ligand-receptor interaction
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