4.6 Article

Platinum (IV) coiled coil nanotubes selectively kill human glioblastoma cells

Journal

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 11, Issue 4, Pages 913-925

Publisher

ELSEVIER
DOI: 10.1016/j.nano.2015.01.014

Keywords

Right handed coiled coil; RHCC; Glioblastoma; Platinum; Prodrug; Nanotubes

Funding

  1. Canada Research Chair program
  2. NSERC
  3. Dept. of Surgery Research Fund
  4. Cancer Research Society

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Malignant glioma are often fatal and pose a significant therapeutic challenge. Here we have employed alpha-helical right handed coiled coils (RHCC) which self-assemble into tetrameric nanotubes that stably associate with platinum (Pt) (IV) compound. This Pt(IV)-RHCC complex showed superior in vitro and in vivo toxicity in human malignant glioma cells at up to 5 fold lower platinum concentrations when compared to free Pt(IV). Pt(IV)-RHCC nanotubes activated multiple cell death pathways in GB cells without affecting astrocytes in vitro or causing damage to normal mouse brain. This Pt(IV)-RHCC nanotubes may serve as a promising new therapeutic tool for low dose Pt(IV) prodrug application for highly efficient and selective treatment of human brain tumors. (C) 2015 Elsevier Inc. All rights reserved.

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