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    Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy

    233051_233051.pdf (1.173Mb)
    Access Status
    Open access
    Authors
    Mo, J.
    Eggers, P.
    Chen, X.
    Ahamed, M.
    Becker, Thomas
    Lim, L.
    Raston, C.
    Date
    2015
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Mo, J. and Eggers, P. and Chen, X. and Ahamed, M. and Becker, T. and Lim, L. and Raston, C. 2015. Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy. Scientific Reports. 5 (Article number: 10414): pp. 1-9.
    Source Title
    Scientific Reports
    DOI
    10.1038/srep10414
    School
    Nanochemistry Research Institute
    Remarks

    This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by/4.0/

    URI
    http://hdl.handle.net/20.500.11937/43632
    Collection
    • Curtin Research Publications
    Abstract

    Vesicles 107 ± 19 nm in diameter, based on the self-assembly of tetra-para-phosphonomethyl calix[4]-arene bearing n-hexyl moieties attached to the phenolic oxygen centres, are effective in binding carboplatin within the cavity of the macrocycle under shear induced within a dynamic thin film in a continuous flow vortex fluidic device. Post shearing the vesicles maintain similar diameters and retain carboplatin within the cavity of the calixarene in a hierarchical structure, with their size and morphology investigated using DLS, TEM, SEM and AFM. Location of the carboplatin was confirmed using NMR, FTIR, ESI-MS and EFTEM, with molecular modelling favouring the polar groups of carboplatin hydrogen bonded to phosphonic acid moieties and the four member cyclobutane ring directed into the cavity of the calixarene. The loading efficiency and release profile of carboplatin was investigated using LC-TOF/MS, with the high loading of the drug achieved under shear and preferential released at pH 5.5, offering scope for anti-cancer drug delivery. The hierarchical structured vesicles increase the efficacy of carboplatin by 4.5 fold on ovarian cancer cells, lowered the IC<inf>50</inf> concentration by 10 fold, and markedly increased the percent of cells in the S-phase (DNA replication) of the cell cycle.

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