Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo.

Haggag, Yusuf A, Matchett, Kyle B, Falconer, Robert A, Isreb, Mohammad, Jones, Jason, Faheem, Ahmed, McCarron, Paul and El-Tanani, Mohamed (2019) Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo. Cancers, 11 (2). ISSN 2072-6694

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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 -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.

Item Type: Article
Additional Information: ** From PubMed via Jisc Publications Router ** History: received 29-12-2018; revised 31-01-2019; accepted 11-02-2019.
Uncontrolled Keywords: Ran, Ran-RCC1 peptide, anti-cancer, anti-metastatic, breast cancer, drug delivery, lung cancer, nanoparticle
Divisions: Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences
SWORD Depositor: Publication Router
Depositing User: Publication Router
Date Deposited: 10 Mar 2020 11:01
Last Modified: 10 Mar 2020 11:01
URI: http://sure.sunderland.ac.uk/id/eprint/10435
ORCID for Robert A Falconer: ORCID iD orcid.org/0000-0002-6426-4430
ORCID for Mohammad Isreb: ORCID iD orcid.org/0000-0003-4042-3940

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