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

Abstract

Targeted and efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, we report a temperature and pH dual responsive core-shell nanoparticles comprising smart polymer shell coated on magnetic nanoparticles as an anticancer drug carrier and cancer cell-specific targeting agent. Magnetite nanoparticles (MNPs), prepared by a simple coprecipitation method, was surface modified by introducing amine groups using 3-aminopropyltriethoxysilane. Dual-responsive poly(N-isopropylacrylamide)-block-poly(acrylic acid) copolymer, synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, was then attached to the amine-functionalized MNPs via EDC/NHS method. Further, to accomplish cancer-specific targeting properties, folic acid was tethered to the surface of the nanoparticles. Thereafter, rhodamine B isothiocyanate was conjugated to endow fluorescent property to the MNPs required for cellular imaging applications. The nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), zeta potential, vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS) measurements, and FTIR, UV-vis spectral analysis. Doxorubicin (DOX), an anticancer drug used for the present study, was loaded into the nanoparticles and its release behavior was subsequently studied. Result showed a sustained release of DOX preferentially at the desired lysosomal pH and temperature condition. The biological activity of the DOX-loaded MNPs was studied by MTT assay, fluorescence microscopy, and apoptosis. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into cancer cells (HeLa cells) compared to normal fibroblast cells (L929 cells). The in vitro apoptosis study revealed that the DOX-loaded nanoparticles caused significant death to the HeLa cells. These nanoparticles were capable of target specific release of the loaded drug in response to pH and temperature and hence may serve as a potential drug carrier for in vivo applications.

Liposome as nanocarrier: Site targeted delivery in lung cancer

“…Different biological uses as medicine and gene delivery, specific cell detection, disparity perfection in magnetic resonance imaging (MRI), bio separation, tissue repair, magnetofection, hyperthermia, etc. are making headway as they are appropriate due to their superparamagnetic nature and biocompatibility [15]. Polymeric self-assemblies constitute smart nanocarriers.…”

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

“…Intracellular uptake of this nanoparticle was monitored using fluorescence microscopy. Furthermore, this smart nanodrug delivery system was capable of targeted stimulus-responsive release of doxorubicin inciting significant cytotoxicity toward the human cervical cancer cell line HeLa (103). Multifunctional nanoparticles are thus expected to overcome some of the conventional obstacles in cancer drug delivery and imaging with an ultimate aim to improve patient care.…”

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“…According to their results, these nanoparticles were taken up specifically by HeLa cancer cells in comparison to normal cells. Their studies revealed that the outer polymer shell encapsulates large amount of anticancer drug Doxorubicin, and releases the anticancer drug preferably at pH 5.0 and temperature 37°C and also they reported the loading amount and entrapment efficiency as 23.0% and 74.4% respectively [5] (Figure 4). Jiang et al [7] reported the designing and preparation of the pH-sensitive magnetic nanoparticles (MNPs) as targeted anticancer drug carriers.…”

“…For instance, the tumor extracellular environment has pH 6.5 which is more acidic than blood and normal tissues (pH 7.4), and endosome and lysosome are even more acidic (pH 5.0 -5.5) [4]. To date diverse pH-responsive delivery systems have been designed and developed for pHtriggered drug delivery [5].…”

“…Wang et al [5] designed a tailor-made dual pH-sensitive polymer drug conjugate nanoparticulate system to overcome the challenges existed in cancer therapy due to drug resistance and inefficient cellular uptake. They reported the capability of their fabricated nanoparticle to reverse surface charge from negative to positive at tumor extracellular pH (∼6.8) to facilitate cell internalization.…”