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

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.

LanguageEnglish
Pages20366-20376
Number of pages11
JournalNanoscale
Volume10
Issue number43
Early online date18 Oct 2018
DOIs
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)

Cite this

Codelivery of a cytotoxin and photosensitiser : Via a liposomal nanocarrier: A novel strategy for light-triggered cytosolic release. / Yaghini, Elnaz; Dondi, Ruggero; Edler, Karen J.; Loizidou, Marilena; Macrobert, Alexander J.; Eggleston, Ian M.

In: Nanoscale, Vol. 10, No. 43, 21.11.2018, p. 20366-20376.

Research output: Contribution to journalArticle

Yaghini, Elnaz ; Dondi, Ruggero ; Edler, Karen J. ; Loizidou, Marilena ; Macrobert, Alexander J. ; Eggleston, Ian M. / Codelivery of a cytotoxin and photosensitiser : Via a liposomal nanocarrier: A novel strategy for light-triggered cytosolic release. In: Nanoscale. 2018 ; Vol. 10, No. 43. pp. 20366-20376.
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