Structure Modification of Magnetite (Fe3o4)-Crosslinked Dextran Nanoparticles for Cellular Uptake Optimization

Magnetic Fluid Hyperthermia or Magnetocytolysis refers to the destruction of cancerous cells loaded with magnetic nanoparticles upon the application of an oscillating magnetic field, resulting in a local temperature increase and providing a possibility for tumor remission. Plasma half-life of the magnetic nanoparticles in the blood stream depends on the size and surface characteristics of the injected particles. In order to promote cellular uptake, the magnetic nanoparticles must be functionalized with a biocompatible material. Optimization of the cellular uptake is being studied by attaching RGD peptides and/or folic acid (FA) to the crosslinked dextran coated nanoparticles. RGD peptides will target particles to the cell membrane and folic acid will increase nanoparticles uptake. Previously we have studied the synthesis of magnetite (Fe3O4) nanoparticles functionalized with crosslinked dextran for magnetic fluid hyperthermia in human colon cancer cells (CaCo-2). We are currently modifying nanoparticle structure by attaching FA and/or RGD peptides to the crosslinked dextran trough amine groups. Attachment of the RGD pepide and/or FA will be achieved by activating their carboxy terminal with dicyclohexylcarbodiimide (DCC), using pyridine and dimethylsulfoxide (DMSO) as solvents. After the carboxy terminal is activated it is ready to form hydrogen bonds to the amine group of the nanoparticles. X-Ray diffraction analysis was performed to characterize the structure of the nanoparticles and measured a crystallite size of 12 nm. FTIR spectroscopy revealed characteristic bands of amine groups in our nanoparticles. SQUID magnetometry was used to measure the DC magnetization response of the nanoparticles, indicating a magnetic core diameter of approximately 10 nm and superparamagnetic behavior at room temperature. Viability and apoptosis of CaCo-2 cell culture in contact with magnetite-crossliked dextran nanoparticles were determined; no cytotoxic effects were observed.

Keywords: magnetocytolysis, magnetite, dextran, RGD peptide, folic acid, nanoparticles, superparamagnetic, cytotoxicity