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Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity.
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; Hiscock, Jennifer R.
Afiliação
  • Dora NO; School of Biosciences, University of Kent Canterbury Kent CT2 7NJ UK M.D.Garrett@Kent.ac.uk.
  • Blackburn E; School of Biosciences, University of Kent Canterbury Kent CT2 7NJ UK M.D.Garrett@Kent.ac.uk.
  • Boles JE; School of Biosciences, University of Kent Canterbury Kent CT2 7NJ UK M.D.Garrett@Kent.ac.uk.
  • Williams GT; School of Physical Sciences, University of Kent Canterbury Kent CT2 7NH UK J.R.Hiscock@Kent.ac.uk.
  • White LJ; School of Physical Sciences, University of Kent Canterbury Kent CT2 7NH UK J.R.Hiscock@Kent.ac.uk.
  • Turner SEG; School of Chemistry, University of Birmingham Edgbaston Birmingham West Midlands B15 2TT UK.
  • Hothersall JD; School of Physical Sciences, University of Kent Canterbury Kent CT2 7NH UK J.R.Hiscock@Kent.ac.uk.
  • Askwith T; Domainex, Chesterford Research Park Saffron Walden CB10 1XL UK.
  • Doolan JA; Domainex, Chesterford Research Park Saffron Walden CB10 1XL UK.
  • Mulvihill DP; Domainex, Chesterford Research Park Saffron Walden CB10 1XL UK.
  • Garrett MD; School of Biosciences, University of Kent Canterbury Kent CT2 7NJ UK M.D.Garrett@Kent.ac.uk.
  • Hiscock JR; School of Physical Sciences, University of Kent Canterbury Kent CT2 7NH UK J.R.Hiscock@Kent.ac.uk.
RSC Adv ; 11(23): 14213-14217, 2021 Apr 13.
Article em En | MEDLINE | ID: mdl-35423951
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.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article