Thermal and pH Responsive Polymer-Tethered Multifunctional\nMagnetic Nanoparticles for Targeted Delivery of Anticancer Drug

Abstract

Targeted and efficient delivery of\ntherapeutics to tumor cells is one of the key issues in cancer therapy.\nIn the present work, we report a temperature and pH dual responsive\ncore–shell nanoparticles comprising smart polymer shell coated\non magnetic nanoparticles as an anticancer drug carrier and cancer\ncell-specific targeting agent. Magnetite nanoparticles (MNPs), prepared\nby a simple coprecipitation method, was surface modified by introducing\namine groups using 3-aminopropyltriethoxysilane. Dual-responsive poly­(<i>N</i>-isopropylacrylamide)-<i>block</i>-poly­(acrylic\nacid) copolymer, synthesized by reversible addition-fragmentation\nchain transfer (RAFT) polymerization, was then attached to the amine-functionalized\nMNPs via EDC/NHS method. Further, to accomplish cancer-specific targeting\nproperties, folic acid was tethered to the surface of the nanoparticles.\nThereafter, rhodamine B isothiocyanate was conjugated to endow fluorescent\nproperty to the MNPs required for cellular imaging applications. The\nnanoparticles were characterized by X-ray diffraction (XRD), transmission\nelectron microscopy (TEM), selected area electron diffraction (SAED),\nfield emission scanning electron microscopy (FESEM), energy-dispersive\nX-ray spectroscopy (EDX), thermogravimetric analysis (TGA), zeta potential,\nvibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy\n(XPS) measurements, and FTIR, UV–vis spectral analysis. Doxorubicin\n(DOX), an anticancer drug used for the present study, was loaded into\nthe nanoparticles and its release behavior was subsequently studied.\nResult showed a sustained release of DOX preferentially at the desired\nlysosomal pH and temperature condition. The biological activity of\nthe DOX-loaded MNPs was studied by MTT assay, fluorescence microscopy,\nand apoptosis. Intracellular-uptake studies revealed preferential\nuptake of these nanoparticles into cancer cells (HeLa cells) compared\nto normal fibroblast cells (L929 cells). The <i>in vitro</i> apoptosis study revealed that the DOX-loaded nanoparticles caused\nsignificant death to the HeLa cells. These nanoparticles were capable\nof target specific release of the loaded drug in response to pH and\ntemperature and hence may serve as a potential drug carrier for <i>in vivo</i> applications.