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Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo.

Publication ,  Journal Article
MacDonald, TJ; Liu, J; Yu, B; Malhotra, A; Munson, J; Park, JC; Wang, K; Fei, B; Bellamkonda, R; Arbiser, J
Published in: Cancers
March 2021

Sonic hedgehog subtype of medulloblastoma (SHH MB) with metastasis or specific clinical or molecular alteration shas a poor prognosis and current therapy results in long-term cognitive impairment in the majority of survivors. Thus, a great need exists for new targeted therapeutic approaches to more effectively treat SHH MB in children. Imipramine blue (IB), a novel molecule with anti-tumor properties, inhibits the NADPH oxidase (NOX) family of enzymes, which are critical for SHH MB survival and treatment resistance. In this study, IB was encapsulated within a liposome to form a liposomal nanoparticle, Liposome-IB (Lipo-IB). This complex has the ability to cross the blood-brain barrier and be preferentially taken up by tumor cells within the brain. We demonstrated in vitro that Lipo-IB treatment caused a dose-dependent decrease in SHH MB cell viability and migration. Short-term administration of single agent Lipo-IB treatment of SHH MB in vivo significantly inhibited tumor growth, reduced the tumor volume, including a complete tumor response, and improved survival compared to control treated mice, without any observable toxicity. We conclude that Lipo-IB is a potential novel nanoparticle-based therapeutic for the treatment of SHH MB that warrants further preclinical safety and efficacy testing for development towards clinical investigation.

Duke Scholars

Published In

Cancers

DOI

EISSN

2072-6694

ISSN

2072-6694

Publication Date

March 2021

Volume

13

Issue

6

Start / End Page

1220

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
MacDonald, T. J., Liu, J., Yu, B., Malhotra, A., Munson, J., Park, J. C., … Arbiser, J. (2021). Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo. Cancers, 13(6), 1220. https://doi.org/10.3390/cancers13061220
MacDonald, Tobey J., Jingbo Liu, Bing Yu, Anshu Malhotra, Jenny Munson, Jaekeun C. Park, Kenty Wang, Baowei Fei, Ravi Bellamkonda, and Jack Arbiser. “Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo.Cancers 13, no. 6 (March 2021): 1220. https://doi.org/10.3390/cancers13061220.
MacDonald TJ, Liu J, Yu B, Malhotra A, Munson J, Park JC, et al. Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo. Cancers. 2021 Mar;13(6):1220.
MacDonald, Tobey J., et al. “Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo.Cancers, vol. 13, no. 6, Mar. 2021, p. 1220. Epmc, doi:10.3390/cancers13061220.
MacDonald TJ, Liu J, Yu B, Malhotra A, Munson J, Park JC, Wang K, Fei B, Bellamkonda R, Arbiser J. Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo. Cancers. 2021 Mar;13(6):1220.

Published In

Cancers

DOI

EISSN

2072-6694

ISSN

2072-6694

Publication Date

March 2021

Volume

13

Issue

6

Start / End Page

1220

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis