Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • MacDonald, TJ; Liu, J; Yu, B; Malhotra, A; Munson, J; Park, JC; Wang, K; Fei, B; Bellamkonda, R; Arbiser, J

Published Date

  • March 11, 2021

Published In

Volume / Issue

  • 13 / 6

Start / End Page

  • 1220 -

PubMed ID

  • 33799550

Pubmed Central ID

  • PMC8001973

Electronic International Standard Serial Number (EISSN)

  • 2072-6694

International Standard Serial Number (ISSN)

  • 2072-6694

Digital Object Identifier (DOI)

  • 10.3390/cancers13061220

Language

  • eng