SECTION: Chemistry
SCIENTIFIC ORGANIZATION:
Lomonosov Moscow State University, Moscow, Russia; Helmholtz Institute for Eye Disease, Moscow, Russia; Center for Social and Forensic Psychiatry, Moscow, Russia; Russian State Medical University, Moscow, Russia;M.M. Shemyakin and Yu.A. Ovchinnikov Institute of bioorganic chemistry RAS, Moscow, Russia;National University of Science and Technology MISiS, Moscow, Russia; Derzhavin Tambov State University,Tambov, Russia; Eshelman School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, USA
REPORT FORM:
«Oral report»
AUTHOR(S)
OF THE REPORT:
N.L. Klyachko, E.A. Zaitseva, E.N. Efremenko, O.A. Kost, N.B. Chesnokova, N.V. Nukolova, L.Yu. Filatova, S.A. Legotsky, K.A. Miroshnikov, A.G. Majouga, Yu.I. Golovin, A.V. Kabanov
SPEAKER:
N.L. Klyachko
REPORT TITLE:
FUNCTIONAL NANOSYSTEMS FOR PHARMACOLOGY AND MEDICINE
TALKING POINTS:

In 2010, the Laboratory of Chemical Design of Bionanomaterials was established at the Lomonosov Moscow State University. Main activities of the laboratory were directed to fundamentals and applications of new classes of bionanosystems based on proteins, enzymes, polymer coatings, magnetic nanoparticles for treatment and diagnostics of a number of diseases of the central nervous system, brain, neurotoxic injury, eye inflammations, bacterial infections, etc.

Using the technology of NanoZYMES™ for therapeutic proteins immobilization and functions (USP WO №2008/141155 A1), novel types of nanomateroials developed. Among them:

Organophosphate hydrolase containing nanozymes possessing the ability to decompose organophosphorus neurotoxins were developed and studied on chemical warfare agents and pesticides in vivo using different ways of administration into the body: intravenously, intramuscularly, intraperitoneally and buccally. As revealed, it is possible to use these formulations both as effective antidotes and protectants. The absence of cytotoxicity and immunogenicity was shown. As found, the dosage of these formulations can be lowered be dozens of times comparing to the conventional antidotes used worldwide.

New formulations of antioxidant nanozymes based on superoxide dismutase were developed and used for eye inflammation and spinal cord injury treatments. Significant improvement in the course of immunogenic uveitis was shown on rabbits. Histological studies have proved the clinical and biochemical data. These results demonstrate high potential therapeutic efficacy of SOD1 nanozyme to treat a wide range of inflammatory diseases in the eye. SOD1 nanozymes were shown to be safe in terms of survival rate for animals with spinal cord injury, and their administration improved recovery dynamics of rat’s voluntary movements.

Bacteriolytic nanozymes effective against Gram-positive and Gram-negative bacteria were prepared and used as antibacterial agents. As an example, nanocompositions of enzymes from bacteriophage phi 11 and K with block-copolymers, effectively lysing of antibiotic resistant strains of Staphylococcus aureus, having high stability and decreased (2-10 times) toxicity, were investigated and characterized.

Hybrid nanomaterials containing enzymes and superparamagnetic nanoparticles with a magnetic core and a gold shell were designed. Effects of low frequency magnetic fields on the conformation and the catalytic activity of enzymes attached to the surface of magnetic nanoparticles, which is the first example of a mechanical-magnetic effect in nanobiocatalysis, have been studied. These studies offer the possibility of using superparamagnetic materials for remote monitoring the different biochemical processes.


The work was supported by grants from Ministry of Education and Science of the Russian Federation (grants 11.G34.000 and K1-2014-022), and from Russian Science Foundation (RSF grant 14-13-00731).