(648b) EGF Conjugated Magnetic Nanoparticles for EGFR Targeted Magnetic Fluid Hyperthermia

Magnetic nanoparticles have the ability to dissipate energy under an oscillating magnetic field, causing a rise in temperature that translates into a decrease in cell viability. This phenomenon is being explored as an alternative treatment to eradicate localized cancer tumors by what is referred to as magnetic fluid hyperthermia (MFH). Magnetic nanoparticles have been used successfully for MFH; however, these nanoparticles typically possess non-specific binding affinity that correlates with lack of specificity and low internalization rates. In order to increase the specificity and efficiency of internalization to specific cell-types, epidermal growth factor (EGF) was conjugated to colloidally stable carboxymethyl dextran (CMDx) coated iron oxide (IO) magnetic nanoparticles to obtain magnetic nanoparticles that target the epidermal growth factor receptor (EGFR), which is overexpressed in many types of cancer such as breast, colon, pancreas, head, and neck. Both targeted and nontargeted nanoparticles were incubated with cancer cells that either overexpress or do not overexpress EGFR. Internalization of targeted nanoparticles was studied as a function of time in both cell lines. Targeted nanoparticles were internalized in both cell lines but with a higher internalization rate in cells that overexpress EGFR. Nanoparticle localization within the cell was visualized by confocal laser scanning showing that targeted magnetic nanoparticles were rapidly accumulated in both flask-shaped small vesicles and large circular endocytic structures. Internalization patterns suggest that both clathrin-dependent and clathrin-independent receptor mediated endocytosis mechanisms are responsible for nanoparticle internalization. Cells were treated by MFH after incubation with targeted and nontargeted nanoparticles. Cells in contact with targeted nanoparticles showed a higher decrease in cell viability after MFH, as compared to cells that underwent MFH after being in contact with nontargeted nanoparticles.