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

Thatchawan Thanasupawat; Hugo Bergen; Sabine Hombach-Klonisch; Jerry Krcek; Saeid Ghavami; Marc R Del Bigio; Sherry Krawitz; Gerald Stelmack; Andrew Halayko; Matthew McDougall; Markus Meier; Jörg Stetefeld; Thomas Klonisch

doi:10.1016/j.nano.2015.01.014

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

Nanomedicine. 2015 May;11(4):913-25. doi: 10.1016/j.nano.2015.01.014. Epub 2015 Feb 11.

Authors

Affiliations

¹ Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
² Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Obstetrics, Gynecology and Reproductive Medicine, University of Manitoba, Winnipeg, MB, Canada.
³ Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Surgery, University of Manitoba, Winnipeg, MB, Canada.
⁴ Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Pathology, University of Manitoba, Winnipeg, MB, Canada.
⁵ Dept. of Pathology, University of Manitoba, Winnipeg, MB, Canada.
⁶ Dept. of Physiology, University of Manitoba, Winnipeg, MB, Canada.
⁷ Dept. of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
⁸ Dept. of Chemistry, University of Manitoba, Winnipeg, MB, Canada; Dept. of Biochemistry and Medical Genetics, Winnipeg, MB, Canada.
⁹ Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Surgery, University of Manitoba, Winnipeg, MB, Canada; Dept. of Medical Microbiology & Infectious Diseases, Winnipeg, MB, Canada; Dept. of Human Anatomy and Cell Science, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada. Electronic address: thomas.klonisch@med.umanitoba.ca.

PMID: 25680541
DOI: 10.1016/j.nano.2015.01.014

Abstract

Malignant glioma are often fatal and pose a significant therapeutic challenge. Here we have employed α-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.

From the clinical editor: The prognosis of malignant glioma remains poor despite medical advances. Platinum, one of the chemotherapeutic agents used, has significant systemic side effects. In this article, the authors employed α-helical right handed coiled coil (RHCC) protein nanotubes as a carrier for cisplatin. It was shown that the new compound achieved higher tumor kill rate but lower toxicity to normal cells and thus may hold promise to be a highly efficient treatment for the future.

Keywords: Glioblastoma; Nanotubes; Platinum; Prodrug; RHCC; Right handed coiled coil.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Astrocytes / metabolism
Astrocytes / pathology
Brain Neoplasms / drug therapy*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Cell Death / drug effects
Cell Line, Tumor
Glioblastoma / drug therapy*
Glioblastoma / metabolism
Glioblastoma / pathology
Humans
Mice
Nanotubes / chemistry*
Platinum Compounds / chemistry
Platinum Compounds / pharmacology*
Prodrugs / chemistry
Prodrugs / pharmacology*

Substances

Antineoplastic Agents
Platinum Compounds
Prodrugs