Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach.
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 r(2) 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 24h 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.
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Chen
C
Fang
Forrest M
FM
Kievit
Omid
O
Veiseh
Zachary R
ZR
Stephen
Tingzhong
T
Wang
Donghoon
D
Lee
Richard G
RG
Ellenbogen
Miqin
M
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000191:economics / Q000379:methods; D011108:Polymers / Q000737:chemistry*; D051381:Rats
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D011108:Polymers; C507253:poly(beta-amino ester); C000499:ferric oxide; D004317:Doxorubicin