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 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.