Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach

Chen Fang, Forrest M. Kievit, Omid Veiseh, Zachary R. Stephen, Tingzhong Wang, Donghoon Lee, Richard G. Ellenbogen, Miqin Zhang

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Nanoparticle-based cancer therapeutics promises to improve drug delivery safety and efficacy. However, fabrication of consistent theranostic nanoparticles with high and controllable drug loading remains a challenge, primarily due to the cumbersome, multi-step synthesis processes conventionally applied. Here, we present a simple and highly controllable method for assembly of theranostic nanoparticles, which may greatly reduce batch-to-batch variation. The major components of this nanoparticle system include a superparamagnetic iron oxide nanoparticle (SPION), a biodegradable and pH-sensitive poly (beta-amino ester) (PBAE) copolymer, a chemotherapeutic agent doxorubicin (DOX). Here the polymer pre-loaded with drug is directly assembled to the surface of SPIONs forming a drug loaded nanoparticle (NP-DOX). NP-DOX demonstrated a high drug loading efficiency of 679 μg DOX per mg iron, sustained stability in cell culture media up to 7 days, and a strong r2 relaxivity of 146 mM- 1•s- 1 for magnetic resonance imaging (MRI). The drug release analysis of NP-DOX showed fast DOX release at pH 5.5 and 6.4 (as in endosomal environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release kinetics. In vitro evaluation of NP-DOX efficacy using drug-resistant C6 glioma cells showed a 300% increase in cellular internalization at 24 h post-treatment and 65% reduction of IC50 at 72 h post-treatment when compared to free DOX. These nanoparticles could serve as a foundation for building smart theranostic formulations for sensitive detection through MRI and effective treatment of cancer by controlled drug release.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalJournal of Controlled Release
Volume162
Issue number1
DOIs
StatePublished - Aug 20 2012
Externally publishedYes

Keywords

  • Drug delivery
  • Magnetic resonance imaging
  • Nanoparticles
  • Theranostics

ASJC Scopus subject areas

  • Pharmaceutical Science

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