pH- and thermo-sensitive MTX-loaded magnetic nanocomposites: synthesis,characterization, and in vitro studies on A549 lung cancer cell and MR imaging |
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| Authors: | Masoud Farshbaf Roya Salehi Nasim Annabi Rovshan Khalilov |
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| Affiliation: | 1. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;2. Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;3. National Institute for Medical Research Development (Nimad), Tehran, Iran;4. Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;5. Biomaterials Innovation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA;6. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA;7. Department of Chemical Engineering, Northeastern University, Boston, MA, USA;8. Institute of Radiation Problems, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan;9. Joint Ukrainian-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Baku, Azerbaijan |
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| Abstract: | 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 (r2) of about 0.15?mM?1·ms?1 and a linear relationship between the transverse relaxation rate (R2) 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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| Keywords: | Theranostic nanomedicine magnetic nanoparticles dual-responsive drug delivery lung cancer methotrexate MRI contrast agent |
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