MacDonald, Tobey J.Liu, JingboYu, BingMalhotra, AnshuMunson, Jennifer M.Park, Jaekeun C.Wang, KentyFei, BaoweiBellamkonda, RaviArbiser, Jack2021-03-152021-03-152021-03-11MacDonald, T.J.; Liu, J.; Yu, B.; Malhotra, A.; Munson, J.; Park, J.C.; Wang, K.; Fei, B.; Bellamkonda, R.; Arbiser, J. Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo. Cancers 2021, 13, 1220.http://hdl.handle.net/10919/102717Sonic 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.application/pdfenCreative Commons Attribution 4.0 Internationalmedulloblastomareactive oxygenNox4sonic hedghogArticle - Refereed2021-03-12https://doi.org/10.3390/cancers13061220