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J Biomed Mater Res A. 2018 Jun;106(6):1753-1764. doi: 10.1002/jbm.a.36360. Epub 2018 Feb 23.

Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple-negative breast cancer cells.

Author information

1
AsclepiX Therapeutics, Baltimore, Maryland, 21218.
2
Department of Biomedical Engineering and Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, Maryland, 21231.
3
Translational Tissue Engineering Cancer, Johns Hopkins School of Medicine, Baltimore, Maryland, 21231.
4
Department of Oncology and the Sidney Kimmel Comprehensive Cancer, Johns Hopkins School of Medicine, Baltimore, Maryland, 21231.
5
Departments of Ophthalmology, Neurosurgery, Materials Science and Engineering, Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21231.
6
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, Maryland, 21231.

Abstract

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.

KEYWORDS:

cancer; drug delivery; nanoparticle; peptide; targeting

PMID:
29424479
PMCID:
PMC6035748
[Available on 2019-06-01]
DOI:
10.1002/jbm.a.36360

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