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Novel Ran-RCC1 inhibitory peptide-loaded nanoparticles have anti-cancer efficacy in vitro and in vivo
Haggag, Y.A. Matchett, K.B. Falconer, Robert A. Isreb, Mohammad Jones, Jason Faheem, A. McCarron, P. El-Tanani, Mohamed
Haggag, Y.A.
Matchett, K.B.
Falconer, Robert A.
Isreb, Mohammad
Jones, Jason
Faheem, A.
McCarron, P.
El-Tanani, Mohamed
Publication Date
2019-02
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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Peer-Reviewed
Yes
Open Access status
openAccess
Accepted for publication
2019-02-11
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Abstract
The delivery of anticancer agents to their subcellular sites of action is a significant challenge
for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have
significant potential to be utilised as cancer therapeutics due to their selectivity, high potency
and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1
(Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in
breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid)
PEG-PLGA polymeric nanoparticles (NPs). A modified double emulsion solvent evaporation
technique was used to optimise the physicochemical properties of these peptide-loaded biodegradable
NPs. The anti-cancer activity of peptide-loaded NPs was studied in vitro using Ran-expressing
metastatic breast (MDA-MB-231) and lung cancer (A549) cell lines, and in vivo using Solid Ehrlich
Carcinoma-bearing mice. The anti-metastatic activity of peptide-loaded NPs was investigated using
migration, invasion and colony formation assays in vitro. A PEG-PLGA-nanoparticle encapsulating
N-terminal peptide showed a pronounced antitumor and anti-metastatic action in lung and breast
cancer cells in vitro and caused a significant reduction of tumor volume and associated tumor growth
inhibition of breast cancer model in vivo. These findings suggest that the novel inhibitory peptides
encapsulated into PEGylated PLGA NPs are delivered effectively to interact and deactivate Ran.
This novel Ran-targeting peptide construct shows significant potential for therapy of breast cancer
and other cancers mediated by Ran overexpression.
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Published version
Citation
Haggag YA, Matchett KB, Falconer RA et al (2019) Novel Ran-RCC1 inhibitory peptide-loaded nanoparticles have anti-cancer efficacy in vitro and in vivo. Cancers. 11(2): 222.
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Article