Liposome-imipramine blue inhibits sonic hedgehog medulloblastoma in vivo

Tobey J. Macdonald, Jingbo Liu, Bing Yu, Anshu Malhotra, Jenny Munson, Jaekeun C. Park, Kenty Wang, Baowei Fei, Ravi Bellamkonda, Jack Arbiser

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number1220
Pages (from-to)1-12
Number of pages12
JournalCancers
Volume13
Issue number6
DOIs
StatePublished - Mar 2 2021
Externally publishedYes

Keywords

  • Medulloblastoma
  • Nox4
  • Reactive oxygen
  • Sonic hedghog

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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