Journal
JOURNAL OF CONTROLLED RELEASE
Volume 162, Issue 1, Pages 233-241Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2012.06.028
Keywords
Drug delivery; Magnetic resonance imaging; Nanoparticles; Theranostics
Funding
- NIH [R01CA134213, R01EB006043]
- NCI/NSF IGERT fellowship
- NIH/NCI training grant [T32CA138312]
- Department of Neurological Surgery of the Fourth Affiliated Hospital of China Medical University
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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.
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