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Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release

Yaghini, E; Dondi, R; Edler, KJ; Loizidou, M; MacRobert, AJ; Eggleston, IM; (2018) Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release. Nanoscale , 10 (43) pp. 20366-20376. 10.1039/C8NR04048F. Green open access

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Abstract

Endosomal entrapment is a key issue for the intracellular delivery of many nano-sized biotherapeutics to their cytosolic or nuclear targets. Photochemical internalisation (PCI) is a novel light-based solution that can be used to trigger the endosomal escape of a range of bioactive agents into the cytosol leading to improved efficacy in pre-clinical and clinical studies. PCI typically depends upon the endolysosomal colocalisation of the bioactive agent with a suitable photosensitiser that is administered separately. In this study we demonstrate that both these components may be combined for codelivery via a novel multifunctional liposomal nanocarrier, with a corresponding increase in the biological efficacy of the encapsulated agent. As proof of concept, we show here that the cytotoxicity of the 30 kDa protein toxin, saporin, in MC28 fibrosarcoma cells is significantly enhanced when delivered via a cell penetrating peptide (CPP)-modified liposome, with the CPP additionally functionalised with a photosensitiser that is targeted to endolysosomal membranes. This innovation opens the way for the efficient delivery of a range of biotherapeutics by the PCI approach, incorporating a clinically proven liposome delivery platform and using bioorthogonal ligation chemistries to append photosensitisers and peptides of choice.

Type: Article
Title: Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/C8NR04048F
Publisher version: https://doi.org/10.1039/C8NR04048F
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (http://creativecommons.org/licenses/by/3.0/).
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.ucl.ac.uk/id/eprint/10060558
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