Wang, JT;
Giuntini, F;
Eggleston, IM;
Bown, SG;
MacRobert, AJ;
(2012)
Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate.
Journal of Controlled Release
, 157
(2)
305 - 313.
10.1016/j.jconrel.2011.08.025.
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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.
| Type: | Article |
|---|---|
| Title: | Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate. |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jconrel.2011.08.025 |
| Publisher version: | http://dx.doi.org/10.1016/j.jconrel.2011.08.025 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Cell Line, Tumor, Cell Survival, Cell-Penetrating Peptides, Humans, Light, Neoplasms, Peptide Fragments, Photochemotherapy, Photosensitizing Agents, Porphyrins, tat Gene Products, Human Immunodeficiency Virus |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1335501 |
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