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ssDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival.
Harris, Michael A; Kuang, Huihui; Schneiderman, Zachary; Shiao, Maple L; Crane, Andrew T; Chrostek, Matthew R; Tabaran, Alexandru-Flaviu; Pengo, Thomas; Liaw, Kevin; Xu, Beibei; Lin, Lucy; Chen, Clark C; O'Sullivan, M Gerard; Kannan, Rangaramanujam M; Low, Walter C; Kokkoli, Efrosini.
Afiliação
  • Harris MA; Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.
  • Kuang H; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Schneiderman Z; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Shiao ML; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Crane AT; Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • Chrostek MR; Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • Tabaran AF; Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • Pengo T; Comparative Pathology Shared Resource, Masonic Cancer Center, University of Minnesota, Saint Paul, MN 55108, USA.
  • Liaw K; University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN 55455, USA.
  • Xu B; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Lin L; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Chen CC; Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • O'Sullivan MG; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Kannan RM; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Low WC; Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • Kokkoli E; Comparative Pathology Shared Resource, Masonic Cancer Center, University of Minnesota, Saint Paul, MN 55108, USA.
Sci Adv ; 7(49): eabl5872, 2021 Dec 03.
Article em En | MEDLINE | ID: mdl-34851666
ABSTRACT
Effective treatment of glioblastoma remains a daunting challenge. One of the major hurdles in the development of therapeutics is their inability to cross the blood-brain tumor barrier (BBTB). Local delivery is an alternative approach that can still suffer from toxicity in the absence of target selectivity. Here, we show that nanotubes formed from self-assembly of ssDNA-amphiphiles are stable in serum and nucleases. After bilateral brain injections, nanotubes show preferential retention by tumors compared to normal brain and are taken up by glioblastoma cells through scavenger receptor binding and macropinocytosis. After intravenous injection, they cross the BBTB and internalize in glioblastoma cells. In a minimal residual disease model, local delivery of doxorubicin showed signs of toxicity in the spleen and liver. In contrast, delivery of doxorubicin by the nanotubes resulted in no systemic toxicity and enhanced mouse survival. Our results demonstrate that ssDNA nanotubes are a promising drug delivery vehicle to glioblastoma.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article