Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity
Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity
Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation. Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as next generation cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAs towards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these lead SSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cell membrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediated cytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus either agent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhance the cytotoxic activity of a chemotherapeutic drug in human cancer cells.
14213-14217
Dora, Nova O.
e0be5472-3290-4782-b6d3-2a5e66242cc9
Blackburn, Edith
afd53f1c-b0fe-4090-afa8-880d48b33f63
Boles, Jessica E.
13ce5778-19eb-4276-8328-d865a86f3c2c
Williams, George T.
26810522-92ef-4b61-a766-582bf15be280
White, Lisa J.
66137725-b91a-4157-ba97-56607f2dbadf
Turner, Scarlett E.G.
460ba480-1699-41f6-9f02-8518d07cd437
Hothersall, J. Daniel
79ce1d85-8c0e-40a1-83c2-d8a18c75dfa4
Askwith, Trevor
6bb9f2b9-13e9-456e-b76d-e3a33d85cbb9
Doolan, Jack A.
f28d260b-fced-4959-a29e-ce10a561981f
Mulvihill, Daniel P.
702f83c0-c2e5-48f0-b745-62a7976a248d
Garrett, Michelle D.
3ee60142-b09e-487f-a2fd-5df8e5797887
Hiscock, Jennifer
abaeec63-a57f-42b8-a9a8-56c80da56081
Dora, Nova O.
e0be5472-3290-4782-b6d3-2a5e66242cc9
Blackburn, Edith
afd53f1c-b0fe-4090-afa8-880d48b33f63
Boles, Jessica E.
13ce5778-19eb-4276-8328-d865a86f3c2c
Williams, George T.
26810522-92ef-4b61-a766-582bf15be280
White, Lisa J.
66137725-b91a-4157-ba97-56607f2dbadf
Turner, Scarlett E.G.
460ba480-1699-41f6-9f02-8518d07cd437
Hothersall, J. Daniel
79ce1d85-8c0e-40a1-83c2-d8a18c75dfa4
Askwith, Trevor
6bb9f2b9-13e9-456e-b76d-e3a33d85cbb9
Doolan, Jack A.
f28d260b-fced-4959-a29e-ce10a561981f
Mulvihill, Daniel P.
702f83c0-c2e5-48f0-b745-62a7976a248d
Garrett, Michelle D.
3ee60142-b09e-487f-a2fd-5df8e5797887
Hiscock, Jennifer
abaeec63-a57f-42b8-a9a8-56c80da56081
Dora, Nova O., Blackburn, Edith, Boles, Jessica E., Williams, George T., White, Lisa J., Turner, Scarlett E.G., Hothersall, J. Daniel, Askwith, Trevor, Doolan, Jack A., Mulvihill, Daniel P., Garrett, Michelle D. and Hiscock, Jennifer
(2021)
Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity.
RSC Advances, 2021 (11), .
(doi:10.1039/D1RA02281D).
Abstract
Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation. Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as next generation cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAs towards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these lead SSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cell membrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediated cytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus either agent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhance the cytotoxic activity of a chemotherapeutic drug in human cancer cells.
Text
d1ra02281d
- Version of Record
More information
Accepted/In Press date: 8 April 2021
e-pub ahead of print date: 14 April 2021
Additional Information:
Acknowledgements
GTW and JRH would like to thank the University of Kent GCDC for funding. JEB would like to thank Public Health England and the University of Kent for PhD studentship funding. JRH and LJW would like to thank the UKRI for JRH's Future Leaders Fellowship (MR/T020415/1). MDG and EB would like to thank the E. B. Hutchinson Charitable Trust for the funding of EB's position.
Identifiers
Local EPrints ID: 474153
URI: http://eprints.soton.ac.uk/id/eprint/474153
ISSN: 2046-2069
PURE UUID: 702fbae9-f788-4b6a-8632-c117b78f588b
Catalogue record
Date deposited: 14 Feb 2023 17:42
Last modified: 17 Mar 2024 04:17
Export record
Altmetrics
Contributors
Author:
Nova O. Dora
Author:
Edith Blackburn
Author:
Jessica E. Boles
Author:
George T. Williams
Author:
Lisa J. White
Author:
Scarlett E.G. Turner
Author:
J. Daniel Hothersall
Author:
Trevor Askwith
Author:
Jack A. Doolan
Author:
Daniel P. Mulvihill
Author:
Michelle D. Garrett
Author:
Jennifer Hiscock
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics