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Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity

Dora, Nova Olympia, Blackburn, Edith, Boles, Jessica E., Williams, George T., White, Lisa J., Turner, Scarlett, Hothersall, Trevor, Askwith, Trevor, Doolan, Jack, Mulvihill, Daniel P., and others. (2021) Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity. RSC Advances, . ISSN 2046-2069. (In press) (KAR id:87520)

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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 nextgeneration cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAstowards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these leadSSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cellmembrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediatedcytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus eitheragent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhancethe cytotoxic activity of a chemotherapeutic drug in human cancer cells.

Item Type: Article
Subjects: Q Science
Q Science > QD Chemistry
Q Science > QD Chemistry > QD431 Organic Chemistry- Biochemistry- Proteins, peptides, amino acids
Divisions: Divisions > Division of Natural Sciences > School of Physical Sciences
Depositing User: Jennifer Hiscock
Date Deposited: 09 Apr 2021 10:13 UTC
Last Modified: 12 Apr 2021 08:55 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/87520 (The current URI for this page, for reference purposes)
Mulvihill, Daniel P.: https://orcid.org/0000-0003-2502-5274
Garrett, Michelle D.: https://orcid.org/0000-0002-3939-1673
Hiscock, Jennifer R.: https://orcid.org/0000-0002-1406-8802
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