Journal
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
Volume 44, Issue 3, Pages 452-462Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/03639045.2017.1397686
Keywords
Theranostic nanomedicine; magnetic nanoparticles; dual-responsive drug delivery; lung cancer; methotrexate; MRI contrast agent
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Funding
- Drug Applied Research Centre of Tabriz University of Medical Sciences
- Iranian Nanotechnology Initiative [95/2-1/5]
- National Institute for Medical Research Development (NIMAD) [963246]
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In the current study, we proposed a facile method for fabrication of multifunctional pH- and thermo-sensitive magnetic nanocomposites (MNCs) as a theranostic agent for using in targeted drug delivery and magnetic resonance imaging (MRI). To this end, we decorated Fe3O4 magnetic nanoparticles (MNPs) with N,N-dimethylaminoethyl methacrylate (DMAEMA) and N-isopropylacrylamide (NIPAAm), best known for their pH- and thermo-sensitive properties, respectively. We also conjugated mesoporous silica nanoparticles (MSNs) to polymer matrix acting as drug container to enhance the drug encapsulation efficacy. Methotroxate (MTX) as a model drug was successfully loaded in MNCs (M-MNCs) via surface adsorption onto MSNs and electrostatic interaction between drug and carrier. The pH- and temperature-triggered release of MTX was concluded through the evaluation of in vitro release at both physiological and simulated tumor tissue conditions. Based on in vitro cytotoxicity assay results, M-MNCs significantly revealed higher antitumor activity compared to free MTX. In vitro MR susceptibility experiment showed that M-MNCs relatively possessed high transverse relaxivity (r(2)) of about 0.15mM(-1)ms(-1) and a linear relationship between the transverse relaxation rate (R-2) and the Fe concentration in the M-MNCs was also demonstrated. Therefore, the designed MNCs can potentially become smart drug carrier, while they also can be promising MRI negative contrast agent.
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