Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo

• Type of Material: Article
• Authors: Tobey MacDonald, Emory University; Jingbo Liu, Emory University; Bing Yu, Emory University; Anshu Malhotra, Emory University; Jenny Munson, Fralin Biomedical Research Institute; Jaekeun Park, Emory University; Kenty Wang, Emory University; Baowei Fei, Emory University; Ravi Bellamkonda, Emory University; Jack Arbiser, Emory University
• Language: English
• Date: 2021-03-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers13061220
• Title of Journal or Parent Work: CANCERS
• Volume: 13
• Issue: 6
• Start Page: 1
• End Page: 12
• Grant/Funding Information: This research received no external funding.
• Keywords: sonic hedghog; Nox4; reactive oxygen; Science & Technology; MOLECULAR SUBGROUPS; Life Sciences & Biomedicine; CANCER; medulloblastoma; Oncology; HETEROGENEITY
• Research Categories: Health Sciences, Radiology; Health Sciences, Oncology

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.