pH- and thermo-sensitive MTX-loaded magnetic nanocomposites: synthesis, characterization, and in vitro studies on A549 lung cancer cell and MR imaging

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.

Keywords:

• Theranostic nanomedicine
• magnetic nanoparticles
• dual-responsive drug delivery
• lung cancer
• methotrexate
• MRI contrast agent

Acknowledgements

The authors would like to express their appreciation to the current head presidents of AZARMEHR MRI center, Dr. Masoud Poureisa and Dr. Mohammad hosein Daghighi for their kind support and assistance with this project.

Disclosure statement

The authors declare that they have no competing interests. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was written based on a dataset of Master of Science thesis, registered in Tabriz University of Medical Sciences and financially supported by Drug Applied Research Centre of Tabriz University of Medical Sciences, and Iranian Nanotechnology Initiative [Grant No. 95/2-1/5]. The authors are also grateful for financial support from National Institute for Medical Research Development (NIMAD) [Grant No. 963246].