Design of Multifunctional Magnetic Nanostructures for
Targeted Delivery of Anticancer Drugs

Abstract

The present dissertation entitled, “Design of Multifunctional Magnetic Nanostructures for Targeted Delivery of Anticancer Drugs” is an embodiment of the investigations aimed at developing multifunctional magnetic nanoparticles intended for administration of some leading anticancer drugs and simultaneous monitoring of the treatment by imaging techniques. The possible diagnostic and therapeutic applications of these multifunctional nanosystems have been explored in vitro. The thesis has been divided into seven chapters. Monodispersed amine functionalized MFe2O4 (M= Co, Mn, Ni) spherical nanoassemblies of size 35-50 nm have been prepared following simple solvochemical approach. The synthesis was accomplished by refluxing metal chloride precursors in ethylene glycol in presence of sodium acetate and ethanolamine. Due to large surface area, high density of amine groups and good aqueous dispersion stability these ferrites may serve as potential materials in biomedical application. Further, CoFe2O4 made by this method was conjugated to anticancer drug methotrexate or doxorubincin, marker molecule folic acid and a fluorescent marker molecule rhodamine isothiocyanate to develop a multifunctional nanoparticle. These drug loaded particles shows combined advantages of superparamagnetism, receptor mediated endocytosis and pH sensitive drug release behavior. Magnetic mesoporous amorphous calcium phosphate nanoparticles with a size of 62 nm and abundant – COOH groups on the surface have been prepared by a simple method. The presence of high surface area and large number of carboxylate groups, facilitate the incorporation of platinum pharmacophore cis-diaquadiamine platinum (II), folic acid and rhodamine isothiocyanate within its porous network. The cytotoxicity and internalization efficiency of these nanocarriers have been evaluated on folate receptor overexpressed HeLa cells. These drug loaded nanoagents exhibit elevated cytotoxicity and induce apoptosis in HeLa cells. Furthermore development of theranostic mesoporous hollow silica nanospheres having therapeutic and diagnostic functions has been established. The internal space of the hollow spheres was utilised to clutch the hydrophobic anticancer drug pemetrexed and superparamagnetic CoFe2O4 nanoparticles while the external surface was chemically modified to graspthe platinum pharmacophore CDDP [cis-diaquadiamino platinum (II)], the marker molecule folic acid and the fluorescent dye RITC. Magnetic hollow spheres loaded with multiple therapeutic cargoes as well as magnetic resonance imaging (MRI) contrast agent exhibit enhanced cytotoxicity as compared to individual drugs. Simple inexpensive magnetic mesoporous carbon-based multimodal theranostic nanoagent best owed with magnetic targeting, T2 contrast behavior, fluorescence imaging, high loading and controlled release of the anticancer drug doxorubicin has been developed. Due to surface modification with carboxylic acid groups the nanoparticles are highly stable in aqueous buffer. The dual optical and magnetic properties of the mesoporous spheres may be utilized in advanced imaging technologies to track the curative responses. The transverse relaxivity value (r2) of the drug absorbed particles was found to be 380.25 mM-1S-1.