Surface Modification And Functionalization Of Magnetic Nanoparticles For Applications In Biomedicine

Magnetic nanoparticles have many important biomedical applications. The surface modification to the particles can dramatically influence their application values. Generally speaking, surface modification has the following three functions: (1) controlling the size and morphology of magnetic nanoparticles; (2) adjusting the colloidal stabilities of the particles; (3) delivering bio-functions to magnetic nanoparticles. In this PhD program, we have prepared magnetic naoparticles modified by various small molecules, polymers, and inorganic nanoparticlers. First,we have prepared dextran, aminosilane, citric acid, betaine, and PEI modified particles, and used them to enhance transfecting plasmid DNA into cells in vitro. Then we prepared calcium phosphate-magnetite hybrid materials to deliver and transfect DNA. We also combined gold nanoparticles onto magnetic nanoparticles to make gold-magnetic hybrid materials. We have prepared both stably combined and"cleavable"complexes. Finally, we coated a thermo-sensitive polymer onto the magnetic particles and then used alternating magnetic field to control the aggregation of such particles. Based on these work, we have the following main points of results:(1) The aggregation size of magnetic nanoparticles has dramatic effect on their performances in magnetofection. Only those weakly aggregated particles can successfully enhance gene transfection.(2) If the particles have sufficiently high surface potentials, either positive or negative, they are capable of enhancing the gene delivery of PEI. In magnetofection, the used magnetic nanoparticles don't have to be coated with functional transfection agents. Instead, surface charged particles can also work well. The preparation of magnetic nanoparticles and gene vector can be separated in a magnetofection study. (3) A novel calcium phosphate-magnetite composite nanomaterial has been prepared. In solution of CaCl₂, such material is able to load a large amount of DNA by co-assembling into complex microspheres. The microspheres are broken in the solution of CO₃^2- and release the loaded DNA, which is still available for PCR amplification. Enhanced by magnetic force, the CaP-M is able to effectively transfect plasmids into COS-7 cells in vitro.(4) Au/PEI/Fe₃O₄ nanocomposite has been prepared via in-situ reducing dissolved HAuCl4 by PEI coated magnetic nanoparticles. The composite is capable of specifically capturing biomolecules with thiol groups.(5) We have designed and prepared gold-magnetic composites where two particles are combined by disulfide bonds. The composites can be cleaved byβ-mercaptoethanol in their dispersions, the gold and magnetic beads are thus separated.(6) The colloidal stabilities and magnetic responses of thermosensitive polymer coated magnetic nanoparticlers can be controlled by a remote alternating magnetic field.