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

Santosh K. Misra; Goutam Ghoshal; Manas R. Gartia; Zhe Wu; Arun K. De; Mao Ye; Corinne R. Bromfield; Emery M. Williams; Kuldeep Singh; Krishnarao V. Tangella; Laurie Rund; Klaus Schulten; Lawrence B. Schook; Partha S. Ray; Everette C. Burdette; Dipanjan Pan

doi:10.1021/acsnano.5b05974

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

Santosh K. Misra, Goutam Ghoshal, Manas R. Gartia, Zhe Wu, Arun K. De, Mao Ye, Corinne R. Bromfield, Emery M. Williams, Kuldeep Singh, Krishnarao V. Tangella, Laurie Rund, Klaus Schulten, Lawrence B. Schook, Partha S. Ray, Everette C. Burdette, Dipanjan Pan

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	10695-10718
Number of pages	24
Journal	ACS Nano
Volume	9
Issue number	11
DOIs	https://doi.org/10.1021/acsnano.5b05974
State	Published - Nov 24 2015

Keywords

anticancer prodrug nanobubble
drug repurposing
liver cancer
thermal ablation

ASJC Scopus subject areas

General Materials Science
General Engineering
General Physics and Astronomy

Online availability

10.1021/acsnano.5b05974

Library availability

Discover UIUC Full Text

Cite this

Misra, S. K., Ghoshal, G., Gartia, M. R., Wu, Z., De, A. K., Ye, M., Bromfield, C. R., Williams, E. M., Singh, K., Tangella, K. V., Rund, L., Schulten, K., Schook, L. B., Ray, P. S., Burdette, E. C., & Pan, D. (2015). Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer. ACS Nano, 9(11), 10695-10718. https://doi.org/10.1021/acsnano.5b05974

Misra, SK, Ghoshal, G, Gartia, MR, Wu, Z, De, AK, Ye, M, Bromfield, CR, Williams, EM, Singh, K, Tangella, KV, Rund, L, Schulten, K, Schook, LB, Ray, PS, Burdette, EC & Pan, D 2015, 'Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer', ACS Nano, vol. 9, no. 11, pp. 10695-10718. https://doi.org/10.1021/acsnano.5b05974

@article{feda46e60348417e90c15344de7db135,

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.",

keywords = "anticancer prodrug nanobubble, drug repurposing, liver cancer, thermal ablation",

author = "Misra, {Santosh K.} and Goutam Ghoshal and Gartia, {Manas R.} and Zhe Wu and De, {Arun K.} and Mao Ye and Bromfield, {Corinne R.} and Williams, {Emery M.} and Kuldeep Singh and Tangella, {Krishnarao V.} and Laurie Rund and Klaus Schulten and Schook, {Lawrence B.} and Ray, {Partha S.} and Burdette, {Everette C.} and Dipanjan Pan",

note = "Publisher Copyright: {\textcopyright} 2015 American Chemical Society.",

year = "2015",

month = nov,

day = "24",

doi = "10.1021/acsnano.5b05974",

language = "English (US)",

volume = "9",

pages = "10695--10718",

journal = "ACS Nano",

issn = "1936-0851",

publisher = "American Chemical Society",

number = "11",

}

TY - JOUR

T1 - Trimodal Therapy

T2 - Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer

AU - Misra, Santosh K.

AU - Ghoshal, Goutam

AU - Gartia, Manas R.

AU - Wu, Zhe

AU - De, Arun K.

AU - Ye, Mao

AU - Bromfield, Corinne R.

AU - Williams, Emery M.

AU - Singh, Kuldeep

AU - Tangella, Krishnarao V.

AU - Rund, Laurie

AU - Schulten, Klaus

AU - Schook, Lawrence B.

AU - Ray, Partha S.

AU - Burdette, Everette C.

AU - Pan, Dipanjan

PY - 2015/11/24

Y1 - 2015/11/24

N2 - 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.

AB - 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.

KW - anticancer prodrug nanobubble

KW - drug repurposing

KW - liver cancer

KW - thermal ablation

UR - http://www.scopus.com/inward/record.url?scp=84948404912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948404912&partnerID=8YFLogxK

U2 - 10.1021/acsnano.5b05974

DO - 10.1021/acsnano.5b05974

M3 - Article

C2 - 26435333

AN - SCOPUS:84948404912

SN - 1936-0851

VL - 9

SP - 10695

EP - 10718

JO - ACS Nano

JF - ACS Nano

IS - 11

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Online availability

Library availability

Related links

Fingerprint

Cite this