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

JOURNAL OF CONTROLLED RELEASE

卷:162

Article

Fang, Chen¹  Kievit, Forrest M.¹  Veiseh, Omid¹  Stephen, Zachary R.¹  Wang, Tingzhong⁴  Lee, Donghoon²  Ellenbogen, Richard G.³  Zhang, Miqin^1,2,3 

[1] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA

[2] Univ Washington, Dept Radiol, Seattle, WA 98195 USA

[3] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA

[4] China Med Univ, Affiliated Hosp 4, Dept Neurol Surg, Shenyang 110032, Liaoning, Peoples R China

关键词: Drug delivery;    Magnetic resonance imaging;    Nanoparticles;    Theranostics;   

DOI  :  10.1016/j.jconrel.2012.06.028

来源: Elsevier

【 摘 要 】

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 mu g DOX per mg iron, sustained stability in cell culture media up to 7days, and a strong r(2) relaxivity of 146mM(-1)center dot 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 24h post-treatment and 65% reduction of IC50 at 72h 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. (C) 2012 Elsevier B. V. All rights reserved.

【 授权许可】

Free