title: Dual Carfilzomib and Doxorubicin-Loaded Liposomal Nanoparticles for Synergistic Efficacy in Multiple Myeloma.
abstract: Here, we report the synthesis and evaluation of dual drug-loaded nanoparticles as an effective means to deliver carfilzomib and doxorubicin to multiple myeloma tumor cells at their optimal synergistic ratio. First, various molar ratios of carfilzomib to doxorubicin were screened against multiple myeloma cell lines to determine the molar ratio that elicited the greatest synergy using the Chou-Talalay method. The therapeutic agents were then incorporated into liposomes at the optimal synergistic ratio of 1:1 to yield dual drug-loaded nanoparticles with a narrow size range of 115 nm and high reproducibility. Our results demonstrated that the dual drug-loaded liposomes exhibited synergy in vitro and were more efficacious in inhibiting tumor growth in vivo than a combination of free drugs, while at the same time reducing systemic toxicity. Taken together, this study presents the synthesis and preclinical evaluation of dual drug-loaded liposomes containing carfilzomib and doxorubicin for enhanced therapeutic efficacy to improve patient outcome in multiple myeloma. Mol Cancer Ther; 15(7); 1452-9. ©2016 AACR.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Ashley
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Charissa J
authors.initials: CJ
authors.lastname: Quinlan
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana. Freimann Life Science Center, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Schroeder
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana. Freimann Life Science Center, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Suckow
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Vincenzo J
authors.initials: VJ
authors.lastname: Pizzuti
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana. Advanced Diagnostics and Therapeutics, University of Notre Dame, Notre Dame, Indiana. bbilgicer@nd.edu tkiziltepe@nd.edu.
authors.forename: Tanyel
authors.initials: T
authors.lastname: Kiziltepe
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana. Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana. Advanced Diagnostics and Therapeutics, University of Notre Dame, Notre Dame, Indiana. bbilgicer@nd.edu tkiziltepe@nd.edu.
authors.forename: Basar
authors.initials: B
authors.lastname: Bilgicer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004338:Drug Combinations; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004338:Drug Combinations; D008081:Liposomes; D009842:Oligopeptides; C524865:carfilzomib; D004317:Doxorubicin