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dc.contributor.authorHaggag, Y.A.*
dc.contributor.authorMatchett, K.B.*
dc.contributor.authorDakir, El-Habib*
dc.contributor.authorBuchanan, P.*
dc.contributor.authorOsman, M.A.*
dc.contributor.authorElgizawy, S.A.*
dc.contributor.authorEl-Tanani, Mohamed*
dc.contributor.authorFaheem, A.M.*
dc.contributor.authorMcCarron, P.A.*
dc.date.accessioned2017-02-22T12:04:53Z
dc.date.available2017-02-22T12:04:53Z
dc.date.issued2017-04
dc.identifier.citationHaggag YA, Matchett KB, Dakir E-H et al (2017) Nano-encapsulation of a novel anti-Ran- GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells. International Journal of Pharmaceutics. 521(1-2): 40-53.en_US
dc.identifier.urihttp://hdl.handle.net/10454/11435
dc.descriptionYesen_US
dc.description.abstractRan is a small ras-related GTPase and is highly expressed in aggressive breast carcinoma. Overexpression induces malignant transformation and drives metastatic growth. We have designed a novel series of anti-Ran-GTPase peptides, which prevents Ran hydrolysis and activation, and although they display effectiveness in silico, peptide activity is suboptimal in vitro due to reduced bioavailability and poor delivery. To overcome this drawback, we delivered an anti-Ran-GTPase peptide using encapsulation in PLGA-based nanoparticles (NP). Formulation variables within a double emulsion solvent evaporation technique were controlled to optimise physicochemical properties. NP were spherical and negatively charged with a mean diameter of 182–277 nm. Peptide integrity and stability were maintained after encapsulation and release kinetics followed a sustained profile. We were interested in the relationship between cellular uptake and poly(ethylene glycol) (PEG) in the NP matrix, with results showing enhanced in vitro uptake with increasing PEG content. Peptide-loaded, pegylated (10% PEG)-PLGA NP induced significant cytotoxic and apoptotic effects in MDA-MB-231 breast cancer cells, with no evidence of similar effects in cells pulsed with free peptide. Western blot analysis showed that encapsulated peptide interfered with the proposed signal transduction pathway of the Ran gene. Our novel blockade peptide prevented Ran activation by blockage of regulator of chromosome condensation 1 (RCC1) following peptide release directly in the cytoplasm once endocytosis of the peptide-loaded nanoparticle has occurred. RCC1 blockage was effective only when a nanoparticulate delivery approach was adopted.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.ijpharm.2017.02.006en_US
dc.rights© 2017 Elsevier B.V. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectAnti-Ran-GTPase peptide; Double emulsion; PLGA; Nanoparticle; Breast cancer; Drug deliveryen_US
dc.titleNano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cellsen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-02-01
dc.date.application2017-02-02
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US


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