title: Colloidal aggregation affects the efficacy of anticancer drugs in cell culture.
abstract: Many small molecules, including bioactive molecules and approved drugs, spontaneously form colloidal aggregates in aqueous solution at micromolar concentrations. Though it is widely accepted that aggregation leads to artifacts in screens for ligands of soluble proteins, the effects of colloid formation in cell-based assays have not been studied. Here, seven anticancer drugs and one diagnostic reagent were found to form colloids in both biochemical buffer and in cell culture media. In cell-based assays, the antiproliferative activities of three of the drugs were substantially reduced when in colloidal form as compared to monomeric form; a new formulation method ensured the presence of drug colloids versus drug monomers in solution. We also found that Evans Blue, a dye classically used to measure vascular permeability and to demonstrate the "enhanced permeability and retention (EPR) effect" in solid tumors, forms colloids that adsorb albumin, as opposed to older literature that suggested the reverse.
authors.affiliation: Donnelly Centre, Department of Chemical Engineering & Applied Chemistry, Institute of Biomaterials & Biomedical Engineering, Department of Chemistry, University of Toronto, 160 College Street, Toronto, Ontario M5S3E1, Canada.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Owen
authors.forename: Allison K
authors.initials: AK
authors.lastname: Doak
authors.forename: Pascal
authors.initials: P
authors.lastname: Wassam
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
mesh_terms: D000327:Adsorption; D000418:Albumins / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003102:Colloids / Q000737:chemistry*; D003470:Culture Media / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005070:Evans Blue / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008027:Light; D046911:Macromolecular Substances; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008956:Models, Chemical; D012542:Scattering, Radiation
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D003102:Colloids; D003470:Culture Media; D008024:Ligands; D046911:Macromolecular Substances; D005070:Evans Blue