Discovery and characterization of a high-affinity and high-specificity peptide ligand LXY30 for in vivo targeting of α3 integrin-expressing human tumors
| Autor: | Yan-lei Liu, Eduardo Sanchez, Kit S. Lam, Ivy A. Kekessie, Anisha Mazloom, Ai-Hong Ma, Ruiwu Liu, Diana Lac, Jimmy Tran, Jia Lin, Wenwu Xiao, Fernanda C. Bononi, Tianhong Li, Kevin Yang |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Clinical Sciences Oncology and Carcinogenesis Integrin Medical Biochemistry and Metabolomics Optical imaging Metastasis Flow cytometry 03 medical and health sciences Rare Diseases 0302 clinical medicine In vivo medicine Radiology Nuclear Medicine and imaging α3β1 integrin Cancer Original Research medicine.diagnostic_test biology business.industry medicine.disease Ligand (biochemistry) In vitro Cancer-targeting peptide Brain Disorders 3. Good health Brain Cancer alpha 3 beta 1 integrin 030104 developmental biology 5.1 Pharmaceuticals One-bead one-compound combinatorial peptide library 030220 oncology & carcinogenesis Biotinylation Immunology Cancer research biology.protein Biomedical Imaging Development of treatments and therapeutic interventions business Glioblastoma |
| Zdroj: | EJNMMI Research EJNMMI research, vol 6, iss 1 Xiao, W; Li, T; Bononi, FC; Lac, D; Kekessie, IA; Liu, Y; et al.(2016). Discovery and characterization of a high-affinity and high-specificity peptide ligand LXY30 for in vivo targeting of α3 integrin-expressing human tumors. EJNMMI Research, 6(1), 1-12. doi: 10.1186/s13550-016-0165-z. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/5tq4x0rx |
| ISSN: | 2191-219X |
| DOI: | 10.1186/s13550-016-0165-z |
| Popis: | Background α3β1 integrin is overexpressed in several types of human cancer and is associated with poor prognosis, metastasis, and resistance to cancer treatment. We previously identified a cyclic peptide ligand LXY1 that specifically binds to the α3β1 integrin on human glioblastoma U-87MG cells. Here, we optimized LXY1 through one-bead one-compound combinatorial library screening and site-specific modifications to improve its in vivo binding property. Methods Three bead libraries were synthesized and whole-cell binding assays were performed. The binding capacity of individual peptide ligands against different tumor cells was determined by flow cytometry and confirmed by optical imaging. A complex joining biotinylated ligand with streptavidin-Cy5.5 was used for in vivo target imaging in both subcutaneous and orthotopic U-87MG xenograft mouse models. Results LXY30, a cyclic peptide with the sequence cdG-Phe(3,5-diF)-G-Hyp-NcR, emerged as the most potent and selective ligand for the α3 subunit of α3β1 integrin with improved in vitro and in vivo tumor-targeting effects compared to LXY1 in U-87MG cells. LXY30 is considerably stable in plasma as demonstrated in an in vitro stability study in 90 % human plasma. LXY30 also binds to several other known α3β1 integrin-expressing glioblastoma, lung, and breast cancer cell lines with various affinities. Conclusions Our data support further investigating the role of LXY30 as a human tumor-targeting peptide ligand for systemic and intracranial delivery of imaging agents and cancer therapeutics. Electronic supplementary material The online version of this article (doi:10.1186/s13550-016-0165-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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