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

Elnaz Yaghini, Ruggero Dondi, Karen J. Edler, Marilena Loizidou, Alexander J. Macrobert, Ian M. Eggleston

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20366-20376
Number of pages11
JournalNanoscale
Volume10
Issue number43
Early online date18 Oct 2018
DOIs
Publication statusPublished - 21 Nov 2018

Keywords

  • Animals
  • Cell Line, Tumor
  • Cell Survival/drug effects
  • Cell-Penetrating Peptides/chemistry
  • Cytosol/metabolism
  • Cytotoxins/chemistry
  • Fibrosarcoma/metabolism
  • Light
  • Liposomes/chemical synthesis
  • Maleimides/chemistry
  • Microscopy, Confocal
  • Photosensitizing Agents/chemistry
  • Porphyrins/chemistry
  • Rats
  • Saporins/chemistry

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint Dive into the research topics of 'Codelivery of a cytotoxin and photosensitiser Via a liposomal nanocarrier: A novel strategy for light-triggered cytosolic release'. Together they form a unique fingerprint.

Cite this