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    Novel Ran-RCC1 inhibitory peptide-loaded nanoparticles have anti-cancer efficacy in vitro and in vivo

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    Isreb_et_al_Cancers_Final.pdf (5.194Mb)
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    Publication date
    2019-02
    Author
    Haggag, Y.A.
    Matchett, K.B.
    Falconer, Robert A.
    Isreb, Mohammad
    Jones, Jason
    Faheem, A.
    McCarron, P.
    El-Tanani, Mohamed
    Keyword
    Ran-RCC1 peptide
    Ran
    Nanoparticle
    Breast cancer
    Lung cancer
    Anti-cancer
    Anti-metastatic
    Drug delivery
    Rights
    © 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
    
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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.
    URI
    http://hdl.handle.net/10454/17484
    Version
    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.
    Link to publisher’s version
    https://doi.org/10.3390/cancers11020222
    Type
    Article
    Collections
    Life Sciences Publications

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