Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple-negative breast cancer cells
| Autor: | Jordan J. Green, Jayoung Kim, Esak Lee, Adam C. Mirando, Ron B. Shmueli, Niranjan B. Pandey, Hojjat Bazzazi, Eric M. Bressler, Aleksander S. Popel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biodistribution Materials science biology Integrin technology industry and agriculture Metals and Alloys Biomedical Engineering Cancer 02 engineering and technology 021001 nanoscience & nanotechnology medicine.disease In vitro Biomaterials 03 medical and health sciences Surface coating 030104 developmental biology In vivo Drug delivery Cancer cell Ceramics and Composites medicine Cancer research biology.protein 0210 nano-technology |
| Zdroj: | Journal of Biomedical Materials Research Part A. 106:1753-1764 |
| ISSN: | 1549-3296 1753-1764 |
| DOI: | 10.1002/jbm.a.36360 |
| Popis: | While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show nonspecific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen-IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor-associated integrins with high affinity, which leads to targeted accumulation in tumor tissue. AXT050 conjugated to PLGA-PEG NPs at precisely controlled surface density functions both as a targeting agent to human tumor cells and demonstrates potential for simultaneous antitumorigenic and antiangiogenic activity. These targeted NPs cause inhibition of adhesion and proliferation in vitro when added to human triple-negative breast cancer cells and microvascular endothelial cells through binding to integrin αV β3 . Furthermore, we find an in vivo biphasic relationship between tumor targeting and surface coating density of NPs coated with AXT050. NPs with an intermediate level of 10% peptide surface coating show approximately twofold greater accumulation in tumors and lower accumulation in the liver compared to nontargeted PLGA-PEG NPs in a murine biodistribution model. Display of biomimetic peptides from NP surfaces to both target and inhibit cancer cells has the potential to enhance the activity of cancer nanomedicines. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1753-1764, 2018. |
| Databáze: | OpenAIRE |
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