Temozolomide nanoparticles for targeted glioblastoma therapy

Chen Fang, Kui Wang, Zachary R. Stephen, Qingxin Mu, Forrest M. Kievit, Daniel T. Chiu, Oliver W. Press, Miqin Zhang

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Glioblastoma (GBM) is a deadly and debilitating brain tumor with an abysmal prognosis. The standard therapy for GBM is surgery followed by radiation and chemotherapy with Temozolomide (TMZ). Treatment of GBMs remains a challenge, largely because of the fast degradation of TMZ, the inability to deliver an effective dose of TMZ to tumors, and a lack of target specificity that may cause systemic toxicity. Here, we present a simple method for synthesizing a nanoparticle-based carrier that can protect TMZ from rapid degradation in physiological solutions and can specifically deliver them to GBM cells through the mediation of a tumor-targeting peptide chlorotoxin (CTX). Our nanoparticle, namely NP-TMZ-CTX, had a hydrodynamic size of <100 nm, exhibited sustained stability in cell culture media for up to 2 weeks, and could accommodate stable drug loading. TMZ bound to nanoparticles showed a much higher stability at physiological pH, with a half-life 7-fold greater than that of free TMZ. NP-TMZ-CTX was able to target GBM cells and achieved 2-6-fold higher uptake and a 50-90% reduction of IC50 72 h post-treatment as compared to nontargeted NP-TMZ. NP-TMZ-CTX showed great promise in its ability to deliver a large therapeutic dose of TMZ to GBM cells and could serve as a template for targeted delivery of other therapeutics.

Original languageEnglish (US)
Pages (from-to)6674-6682
Number of pages9
JournalACS Applied Materials and Interfaces
Volume7
Issue number12
DOIs
StatePublished - Apr 1 2015

Keywords

  • MGMT
  • chlorotoxin
  • drug delivery
  • glioblastoma
  • nanomedicine
  • therapeutics

ASJC Scopus subject areas

  • Materials Science(all)

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  • Cite this

    Fang, C., Wang, K., Stephen, Z. R., Mu, Q., Kievit, F. M., Chiu, D. T., Press, O. W., & Zhang, M. (2015). Temozolomide nanoparticles for targeted glioblastoma therapy. ACS Applied Materials and Interfaces, 7(12), 6674-6682. https://doi.org/10.1021/am5092165