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

50 Citations (Scopus)

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

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temozolomide
Tumors
Nanoparticles
Degradation
Chemotherapy
Cell culture
Surgery
Peptides
Toxicity
Brain
Hydrodynamics
Radiation

Keywords

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

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

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

Temozolomide nanoparticles for targeted glioblastoma therapy. / Fang, Chen; Wang, Kui; Stephen, Zachary R.; Mu, Qingxin; Kievit, Forrest M.; Chiu, Daniel T.; Press, Oliver W.; Zhang, Miqin.

In: ACS Applied Materials and Interfaces, Vol. 7, No. 12, 01.04.2015, p. 6674-6682.

Research output: Contribution to journalArticle

Fang, C, Wang, K, Stephen, ZR, Mu, Q, Kievit, FM, Chiu, DT, Press, OW & Zhang, M 2015, 'Temozolomide nanoparticles for targeted glioblastoma therapy', ACS Applied Materials and Interfaces, vol. 7, no. 12, pp. 6674-6682. https://doi.org/10.1021/am5092165
Fang, Chen ; Wang, Kui ; Stephen, Zachary R. ; Mu, Qingxin ; Kievit, Forrest M. ; Chiu, Daniel T. ; Press, Oliver W. ; Zhang, Miqin. / Temozolomide nanoparticles for targeted glioblastoma therapy. In: ACS Applied Materials and Interfaces. 2015 ; Vol. 7, No. 12. pp. 6674-6682.
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