Folic acid conjugated Fe₃O₄ magnetic nanoparticles for targeted delivery of doxorubicin

Abstract

The interfacial engineering of magnetic nanoparticles (MNPs) with specific functional groups or targeting ligands is important for their in vivo applications. We report here the preparation and characterization of bifunctional magnetic nanoparticles (BMNPs) which contain a carboxylic moiety for drug binding and an amine moiety for folate mediated drug targeting. BMNPs were prepared by introducing bioactive cysteine molecules onto the surface of undecenoic acid coated FeO magnetic nanoparticles (UMNPs) via a thiol-ene click reaction and then, folic acid was conjugated with these BMNPs through an EDC-NHS coupling reaction. X-ray diffraction (XRD) and transmission electron microscopy (TEM) analysis indicate the formation of highly crystalline single-phase FeO nanostructures. The changes in the interfacial characteristics of the nanoparticles and the presence of an organic coating are evident from Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta-potential measurement, and thermogravimetric analysis (TGA). These nanocarriers have an average size of 10 nm, and have a pH dependent charge conversional feature and protein resistance characteristic in physiological medium. These nanoparticles also show high loading affinity for an anticancer drug, doxorubicin hydrochloride (DOX) and its pH dependent release. This is highly beneficial for cancer therapy as the relatively low pH in tumors will specifically stimulate the drug release at the site of interest. Furthermore, our fluorescence microscopy and flow cytometry studies confirmed the higher cellular internalization capability of these folic acid conjugated nanoparticles in cancer cells over-expressing folate receptors.

Enzymatic stimuli‐responsive methotrexate‐conjugated magnetic nanoparticles for target delivery to breast cancer cells and release study in lysosomal condition

“…Interest in design and developing nanoparticles (NPs) for applications in catalyst, optics, electronics, and biomedicine has continued to grow in the past decade due to their unique physical and chemical properties . In particular, magnetic nanoparticles (MNPs) have attracted significant attention, mainly in biomedical fields, especially in the development of drug delivery systems that has been one of the major thrust areas of biomedical research …”

“…[1][2][3][4] In particular, magnetic nanoparticles (MNPs) have attracted significant attention, mainly in biomedical fields, especially in the development of drug delivery systems that has been one of the major thrust areas of biomedical research. [5][6][7][8] Bare F 3 O 4 NPs have a large surface area to volume ratio, cause agglomeration of the NPs and formation of clusters, resulting in increased particle size and reduced intrinsic superparamagnetic properties. 9 Thus, surface coating and functionalization of the MNPs is necessary for decreasing the NPs aggregation and for successful uses for technological and biomedical applications.…”

PEGlatyon-SPION surface functionalization with folic acid for magnetic hyperthermia applications

“…In order to ensure the colloidal stability and biodistribution on physiological medium, SPION is frequently functionalized with biocompatible polymers, from a natural source (polysaccharides, such as dextran, chitosan, alginate, etc [19]) to synthetic ones (poly(lactide-co-glycolide) (PLGA) [20], polycaprolactone (PCL) [21] and polyethylene glycol (PEG) [22,23]). PEG shows high water solubility and low cytotoxicity properties.…”

“…Concerning to the selectivity, folate receptors are overexpressed during the disordered growth of tumor cells for the internalization of nutrients required for cell division, such as folic acid [22,[24][25][26]. Chen et al [27] have described the structural basis of recognition of folic acid by folates receptors.…”

Improvement of Anticancer Drug Release by Cobalt Ferrite Magnetic Nanoparticles through Combined pH and Temperature Responsive Technique

“…The drug release spectra were measured under different time interval with the help of UV‐visible spectrometer at two different pH and temperatures. It is clear from the graphs (Figure (a) and 5(b)) that drug release spectra is no doubt better at lower pH and elevated temperature . At higher temperature, due to increase of thermal agitation, the drug molecules started to detach from the surface of the CFMNPs, which helped to increase the drug release rate.…”