Novel Medical Ferrite Nanobeads with Bioactive Molecules Immobilized Strongly onto the Surfaces

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Novel Medical Ferrite Nanobeads with Bioactive Molecules Immobilized Strongly onto the Surfaces Masanori Abe1 , Nobuhiro Matsushita1, Masaru Tada1, Nobuyuki Gokon2, Kosuke Nishio2, and Hiroshi Handa2 1

Department of Physical Electronics, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo152-8552, Japan, 2 Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuda, Midori-ku, Yokohama226-8503, Japan

ABSTRACT Under neutral conditions (pH=7-9) and temperature as low as 4 ℃ we successfully synthesized ferrite nanoparticles with an intermediate structure between Fe3O4 and γ -Fe2O3 from an aqueous solution. These experimental conditions enabled us to immobilize even very unstable bioactive molecules onto the surfaces of the ferrite nanoparticles during their synthesis. The bioactive molecules were strongly fixed onto the ferrite surface intermediated by specific amino-acids or related-structure molecules each having pairs of carboxyl (COOH) groups. The COOH group pair was found to make a chemical bond with the ferrite particles. Utilizing the strong bond between such molecules and ferrites, we successfully prepared bioactive ferrite nanobeads where the ferrite nanoparticles were encapsulated in a polymer that exhibited negligible non-specific absorption of proteins. We also succeeded in fixing bioactive molecules onto the surfaces of the polymer coating of the ferrite nanobeads. We describe promising applications of our novel bioactive ferrite nanobeads such as high performance magnetic

S8.2.2

carriers for bio-screening, hypothermia, MRI contrast enhancement and magnetic drug delivery.

INTRODUCTION The end of the genomic-era has resulted in new scientific challenges in the field of biomedical research. In particular, there are increasing demands for the development of high performance, nanometer sized, polymer-coated magnetic beads for use as carriers for high throughput bio-screening (HTBS) [1]. By HTBS it is possible to collect or purify bio-“receptors” and the “chemicals” (which are also referred to as “ligands”) that are selectively coupled to the bio-receptors. The affinity coupling of receptors and ligands, for example antigens (which cause diseases) and drugs (which cure diseases), control physiological functions in our body. Medicinal effects result due to conformational changes occuring in the receptors when they react with the drugs. The side effects of the drugs occur when they are coupled to receptors other than the targeted ones responsible for the diseases. Therefore, the use of HTBS will enable the elucidation of the mechanisms related to the main and side effects of the drugs, and will thus in turn facilitate development of new drugs based on genetic information from which the receptors can be produced. This technology will open the way to fabricate drugs exhibiting no side effects and finally the realization of “tailored medicine” that affords medical treatments and drugs optimized to individuals according to their genetic information. The principle of HTBS i