| Literature DB >> 26435333 |
Manas R Gartia1, Zhe Wu2, Arun K De3, Mao Ye1, Santosh K Misra1, Goutam Ghoshal4, Corinne R Bromfield5, Emery M Williams4, Kuldeep Singh6, Krishnarao V Tangella7, Laurie Rund3, Klaus Schulten8, Lawrence B Schook1,3, Partha S Ray1,8, Everette C Burdette4, Dipanjan Pan1,8,9,10.
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.Entities:
Keywords: anticancer prodrug nanobubble; drug repurposing; liver cancer; thermal ablation
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Year: 2015 PMID： 26435333 PMCID： PMC4820022 DOI： 10.1021/acsnano.5b05974
Source DB: PubMed Journal: ACS Nano ISSN： 1936-0851 Impact factor: 15.881