Engineered Nanostructures for Active Targeting of Cancerous Tumors

Abstract

The unusual magnetic properties exhibited by superparamagnetic nanoparticles and their promising technological applications have attracted much interest in recent years. The superparamagnetic nanoparticles have applications in the field of nanomedicine ranging from cell separation, hyperthermia to drug delivery. The present thesis is aimed at design and fabrication of magnetic drug delivery system, which is based on active targeting concept. The core of the drug delivery system was comprised of superparamagnetic magnetite nanoparticles. The magnetite nanoparticles were prepared by chemical co-precipitation and thermal decomposition methods. Magnetite nanoparticles have a large surface area/volume ratio and tend to agglomerate to reduce surface energy. To prevent the particle agglomeration we coat magnetite nanoparticles with biocompatible hydrophilic polymer PEG. It was found that the co-precipitation route yield polydisperse system with inferior magnetic properties, while the thermal decomposition route yields monodisperse magnetite with very high saturation magnetization (Ms = 80 emu/g). To provide specificity to the drug delivery system, PEG functionalized magnetite nanoparticles were further modified with folate receptors. This will particularly improve the targeting ability of the system, as the folate receptors are over expressed by most of the cancer tumors and marginally expressed on the surface of healthy cells. The anticancer drug doxorubicin was loaded into the folic acid modified, PEG coated magnetite nanostructures, as doxorubicin is powerful anti-neoplastic drug used for the treatment of wide variety of cancers. The designed drug delivery system and their components were characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy and Vibrating sample magnetometer (VSM). X-ray analysis reveals that the single phase inverse spinel magnetite nanoparticles have been synthesized both by chemical coprecipitation and thermal decomposition routes. However, TEM and VSM measurements indicate that the co-precipitation method yields polydispersed nanoparticles with poor magnetic properties. The loading of doxorubicin was confirmed by UV-spectra while the surface functionalization of magnetite was confirmed by FTIR spectroscopy. The designed drug delivery system can be intravenously injected and could be targeted to the desired site by means of external magnetic field. Further, it is also possible to load multiple anticancer/radiotherapeutic drugs into the same drug delivery system.