title: Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer.
abstract: Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physico-chemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell internalization capability, and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.
authors.affiliation: Department of Bioengineering University of Illinois at Urbana-Champaign, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Misra
authors.affiliation: Acoustic Med System, 208 Burwash Ave, Savoy, Illinois, USA.
authors.forename: Goutam
authors.initials: G
authors.lastname: Ghoshal
authors.affiliation: Department of Bioengineering University of Illinois at Urbana-Champaign, USA.
authors.forename: Manas R
authors.initials: MR
authors.lastname: Gartia
authors.affiliation: Center for the Physics of Living Cells, Department of Physics, University of Illinois at Urbana-Champaign, Illinois, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: De
authors.affiliation: Department of Bioengineering University of Illinois at Urbana-Champaign, USA.
authors.forename: Mao
authors.initials: M
authors.lastname: Ye
authors.affiliation: Agricultural Animal Care and Use Program, University of Illinois at Urbana-Champaign, Illinois, USA.
authors.forename: Corinne R
authors.initials: CR
authors.lastname: Bromfield
authors.affiliation: Acoustic Med System, 208 Burwash Ave, Savoy, Illinois, USA.
authors.forename: Emery M
authors.initials: EM
authors.lastname: Williams
authors.affiliation: Veterinary Diagnostic Laboratory, University of Illinois, Champaign-Urbana, Illinois, USA.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Singh
authors.affiliation: Pathology and Internal Medicine, University of Illinois-Urbana Champaign, Illinois, USA.
authors.forename: Krishnarao V
authors.initials: KV
authors.lastname: Tangella
authors.affiliation: Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Rund
authors.affiliation: Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, Illinois, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
authors.affiliation: Department of Bioengineering University of Illinois at Urbana-Champaign, USA.|Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, USA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schook
authors.affiliation: Department of Bioengineering University of Illinois at Urbana-Champaign, USA.|Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, Illinois, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Ray
authors.affiliation: Acoustic Med System, 208 Burwash Ave, Savoy, Illinois, USA.
authors.forename: Everette C
authors.initials: EC
authors.lastname: Burdette
authors.affiliation: Department of Bioengineering University of Illinois at Urbana-Champaign, USA.|Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, Illinois, USA.|Mills Breast Cancer Institute, Carle Foundation Hospital, 502 N. Busey, Urbana, Illinois, USA.|Department of Materials Science and Engineering, University of Illinois-Urbana Champaign, Illinois, USA.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
mesh_terms: D000818:Animals; D000077610:Bexarotene; D057785:Catheters; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D058492:Drug Repositioning; D004560:Electricity; D004586:Electrophoresis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis / Q000627:therapeutic use; D011789:Quantum Theory; D047490:Retinoid X Receptor alpha / Q000819:agonists / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D034421:Sus scrofa; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000627:therapeutic use*; D013816:Thermodynamics; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D011355:Prodrugs; D047490:Retinoid X Receptor alpha; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene
keywords: anticancer prodrug nanobubble; drug repurposing; liver cancer; thermal ablation