Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo

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dc.contributor.authorMacDonald, Tobey J.en
dc.contributor.authorLiu, Jingboen
dc.contributor.authorYu, Bingen
dc.contributor.authorMalhotra, Anshuen
dc.contributor.authorMunson, Jennifer M.en
dc.contributor.authorPark, Jaekeun C.en
dc.contributor.authorWang, Kentyen
dc.contributor.authorFei, Baoweien
dc.contributor.authorBellamkonda, Ravien
dc.contributor.authorArbiser, Jacken
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2021-03-15T11:43:59Zen
dc.date.available2021-03-15T11:43:59Zen
dc.date.issued2021-03-11en
dc.date.updated2021-03-12T14:40:49Zen
dc.description.abstractSonic 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMacDonald, 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.en
dc.identifier.doihttps://doi.org/10.3390/cancers13061220en
dc.identifier.urihttp://hdl.handle.net/10919/102717en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmedulloblastomaen
dc.subjectreactive oxygenen
dc.subjectNox4en
dc.subjectsonic hedghogen
dc.titleLiposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivoen
dc.title.serialCancersen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Destination Area: Adaptive Brain and Behavior (ABB)
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