Santosh K. Misra, Goutam Ghoshal, Manas R. Gartia, Zhe Wu, Mao Ye, Corinne R.
Bromfield, Emery M. Williams, Krishnarao V. Tangella, Klaus Schulten,
Partha S. Ray, Everette C. Burdette, and Dipanjan Pan.
Tri-Modal therapy: Combining hyperthermia with repurposed
bexarotene and ultrasound for treating liver cancer.
ACS Nano, 9:10695-10718, 2015.
(PMC: PMC4820022)
MISR2015
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 use 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.
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