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Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer

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    Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer
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    † ▲ ▽ †Department of Bioengineering, §Center for the Physics of Living Cells, Department of Physics, ∥Department of Animal Sciences, ⊥Agricultural Animal Care and Use Program, #Veterinary Diagnostic Laboratory, Pathology and Internal Medicine, ▲Beckman Institute of Advanced Science and Technology, and ▽Department of Materials Science and Engineering, University of Illinois at Urbana—Champaign, Champaign, Illinois 61820, United States
    ‡ Acoustic Med System, 208 Burwash Avenue, Savoy, Illinois 61874, United States
    □ Mills Breast Cancer Institute, Carle Foundation Hospital, 502 North Busey, Urbana, Illinois 61801, United States
    *Address correspondence to [email protected], [email protected]
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    ACS Nano

    Cite this: ACS Nano 2015, 9, 11, 10695–10718
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    https://doi.org/10.1021/acsnano.5b05974
    Published October 5, 2015
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    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.

    Copyright © 2015 American Chemical Society

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    • Synthesis of pro-bexarotene, experimental setup for in vitro U.S. studies, Raman spectroscopic details of NB samples, MTT assay experiments, bright-field images of HepG2 cells, experimental setup for ex vivo pig liver tissue, temperature profile of the three thermocouples, and location of the applicators and the flexible needles (PDF)

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    This article is cited by 56 publications.

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    ACS Nano

    Cite this: ACS Nano 2015, 9, 11, 10695–10718
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.5b05974
    Published October 5, 2015
    Copyright © 2015 American Chemical Society
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