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. LU
; Loizidou, Marilena
; MacRobert, Alexander J.
and Eggleston, Ian M.
(2018)
In Nanoscale
10(43).
p.20366-20376
- 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... (More)
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.
(Less)
- author
- Yaghini, Elnaz
; Dondi, Ruggero
; Edler, Karen J.
LU
; Loizidou, Marilena
; MacRobert, Alexander J.
and Eggleston, Ian M.
- publishing date
- 2018-11-21
- type
- Contribution to journal
- publication status
- published
- in
- Nanoscale
- volume
- 10
- issue
- 43
- pages
- 11 pages
- publisher
- Royal Society of Chemistry
- external identifiers
-
- pmid:30376028
- scopus:85056299579
- ISSN
- 2040-3364
- DOI
- 10.1039/c8nr04048f
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2018 The Royal Society of Chemistry.
- id
- d276af6c-3317-40e0-9d4d-7e672006efce
- date added to LUP
- 2023-01-18 09:09:13
- date last changed
- 2024-03-06 11:22:05
@article{d276af6c-3317-40e0-9d4d-7e672006efce,
abstract = {{<p>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.</p>}},
author = {{Yaghini, Elnaz and Dondi, Ruggero and Edler, Karen J. and Loizidou, Marilena and MacRobert, Alexander J. and Eggleston, Ian M.}},
issn = {{2040-3364}},
language = {{eng}},
month = {{11}},
number = {{43}},
pages = {{20366--20376}},
publisher = {{Royal Society of Chemistry}},
series = {{Nanoscale}},
title = {{Codelivery of a cytotoxin and photosensitiser <i>via </i>a liposomal nanocarrier : A novel strategy for light-triggered cytosolic release}},
url = {{http://dx.doi.org/10.1039/c8nr04048f}},
doi = {{10.1039/c8nr04048f}},
volume = {{10}},
year = {{2018}},
}