Magnetic Nanoparticles for Drug / Gene Delivery

Although various drugs have been developed to treat different diseases such as cancer, the therapeutic effects of many drugs have been limited by their undesirable properties such as poor solubility, poor bioactivity, rapid clearance in blood and non-specific distribution. Nanoparticles as carriers have received more and more attention in the last two decades due to their ability of overcoming these obstacles and enhancing the therapeutic efficiency of the conventional drugs. In this thesis, various kinds of nanoparticles were developed aiming at improving the therapeutic efficiency and targeted delivery of anti-cancer drug and gene. Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this thesis, magnetic-polymer core-shell nanoparticles based on non-toxic, biocompatible and biodegradable polymers such as silk fibroin, alginate and chitosan were prepared and optimized to improve the uptake efficiency and cell growth inhibition effect of curcumin towards cancer cells. The size, zeta potential, surface morphology, drug loading / release profile, in vitro uptake and growth inhibition effect to cancer and normal cells of these curcumin loaded nanoparticles were investigated. The results indicated that the curcumin loaded particles exhibited enhanced uptake efficiency and growth inhibition effect on MDA-MB-231 cancer cells compared with free curcumin. Higher uptake efficiency and cytotoxicity to MDA-MB-231 cells than normal human dermal fibroblast cells were observed, suggesting they have specific effects against cancer cells. Moreover, in vitro targeted delivery of curcumin to specific areas of cells was achieved with the presence of an external magnetic field, suggesting these magnetic nanoparticles are promising for targeted delivery of drugs to desired sites applying magnetic forces. Apart from drug delivery the applications of magnetic nanoparticles in gene delivery was also investigated. Polyethyleneimine is one of the most efficient non-viral transfection agents for gene delivery due to its high cationic charge density. In this thesis, silk fibroin was selected to fabricate magnetic-silk / polyethyleneimine core-shell nanoparticles and silk-polyethyleneimine nanoparticles for the transfection of an anticancer gene (c-myc antisense oligodeoxynucleotides) into MDA-MB-231 breast cancer cells and human dermal fibroblast cells. The results illustrated that the cytotoxicity of magnetic-silk / polyethyleneimine core-shell nanoparticles was significantly lower than polyethyleneimine coated magnetic nanoparticles which is widely studied as a gene delivery carrier. The magnetic-silk / polyethyleneimine core-shell nanoparticles were capable of delivering c-myc antisense oligodeoxynucleotides into MDA-MB-231 cells and significantly inhibiting the cell growth. Employing magnetic-silk / polyethyleneimine core-shell nanoparticles, high uptake efficiency of c-myc antisense oligodeoxynucleotides was achieved within 20 min via magnetofection. In addition, magnetic-silk / polyethyleneimine core-shell nanoparticles exhibited higher cytotoxic effect against MDA-MB-231 breast cancer cells than normal human dermal fibroblast. Moreover, in vitro targeted delivery of oligodeoxynucleotides can be achieved using magnetic-silk / polyethyleneimine core-shell nanoparticles under a magnetic field.