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Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate


Reference:

Wang, J. T. -W., Giuntini, F., Eggleston, I. M., Bown, S. G. and MacRobert, A. J., 2012. Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate. Journal of Controlled Release, 157 (2), pp. 305-313.

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    Official URL:

    http://dx.doi.org/10.1016/j.jconrel.2011.08.025

    Abstract

    Photochemical internalisation (PCI) is a site-specific technique for improving cellular delivery of macromolecular drugs. In this study, a cell penetrating peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a porphyrin photosensitiser has been shown to be effective for PCI. Herein we report an investigation of the photophysical and photobiological properties of a water soluble bioconjugate of the cationic Tat peptide with a hydrophobic tetraphenylporphyrin derivative. The cellular uptake and localisation of the amphiphilic bioconjugate was examined in the HN5 human head and neck squamous cell carcinoma cell line. Efficient cellular uptake and localisation in endo/lysosomal vesicles was found using fluorescence detection, and light-induced, rupture of the vesicles resulting in a more diffuse intracellular fluorescence distribution was observed. Conjugation of the Tat sequence with a hydrophobic porphyrin thus enables cellular delivery of an amphiphilic photosensitiser which can then localise in endo/lysosomal membranes, as required for effective PCI treatment. PCI efficacy was tested in combination with a protein toxin, saporin, and a significant reduction in cell viability was measured versus saporin or photosensitiser treatment alone. This study demonstrates that the cell penetrating peptide-photosensitiser bioconjugation strategy is a promising and versatile approach for enhancing the therapeutic potential of bioactive agents through photochemical internalisation.

    Details

    Item Type Articles
    CreatorsWang, J. T. -W., Giuntini, F., Eggleston, I. M., Bown, S. G. and MacRobert, A. J.
    DOI10.1016/j.jconrel.2011.08.025
    DepartmentsFaculty of Science > Pharmacy & Pharmacology
    Publisher StatementEggleston_JCR_2011.pdf: NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Controlled Release. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Controlled Release, vol 157, issue 2, 2011, DOI 10.1016/j.jconrel.2011.08.025
    RefereedYes
    StatusPublished
    ID Code26308

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