Abstract
Polyacrylic acid functionalized Fe3O4 nanoparticles (PAA-MNPs) of average size of 10 nm are prepared by a simple soft chemical approach. These PAA-MNPs are conjugated with folic acid through peptide bonding between the carboxylic group on the surface of PAA-MNPs and the amine group of folic acid. The good colloidal stability of FA conjugated MNPs makes it a promising candidate for targeted drug delivery, hyperthermia and as a MRI contrast agent with a transverse relaxivity R2 value of 105 mM(-1) s(-1). Folic acid conjugated magnetic nanoparticles (FA-MNPs) achieved ∼ 95% loading efficiency of doxorubicin (DOX) which could be due to strong electrostatic interaction of highly negatively charged FA-MNPs and the positively charged DOX. The drug release study shows a pH-dependent behavior and is higher in acidic pH (4.3 and 5.6) as compared to the physiological pH (7.3). Flow cytometry and confocal microscopic image analysis reveal that around 75-80% of HeLa cells undergo apoptosis due to DNA disintegration upon incubation with DOX-MNPs for 24 h. DOX-MNPs exhibit the synergistic effect due to the combination of DOX induced apoptosis and magnetic hyperthermia treatment (MHT) which enhance the cell death ∼ 95.0%. Thus, this system may serve as a potential pH sensitive nanocarrier for synergistic chemo-thermal therapy as well as a possible MRI contrast agent.
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