Research interests
Magnetic nanoparticles; delivery of drugs; diagnostics; oncology.
Field of knowledge according to OECD
Nanomaterials and nanotechnologies.
2017: Karolinska Institute (Sweden), researcher.
2010: University of Nebraska Omaha, Medical Center (USA), exchange training.
Faculty of Chemistry, Lomonosov Moscow State University.
The main trend of modern bionanomedicine is the development of methods to synthesize magnetic nanoparticles (MNP) providing for strict control over the size and form, as well as the ease of surface modification. As of now, MNPs are used as promising means of diagnostics and therapy of socially significant diseases.
Methods of obtaining MNPs based on complex ferrous oxides (magnetite, maghemite, cobalt iron oxide) were developed. Methods of obtaining MNPs of a spherical, cubic and rod-like form with diameters ranging from 6 to-40 nm with narrow monomodal distribution by sizes were also developed. The key advantage of proposed methods is the ease of surface modification with low-molecular ligands and biocompatible polymers. Obtained were MNPs containing: citric acid,
MNPs constitute a universal class of nanomaterials permitting the combination of features of a therapeutic and diagnostic agent in the same drug. We assessed the diagnostic potential. The method of magnetic resonance imaging (MRI) is one of the most frequently used methods of non-invasive diagnostics. For example, for MNPs stabilized by the human serum albumin (MNP-HSA), we demonstrated the efficiency of visualization by the MNP method in respect of different tumors as exemplified by glioblastoma, mammary adenocarcinoma, colon and prostatic carcinoma, etc. In the event of visualizing multi-form glioblastoma, full-scale pre-clinical studies of safety and efficiency were performed for MNPs that attested to the prospects of further clinical tests. For MNP-HSA, experimental-industrial production rules were developed, and an experimental batch was prepared in accordance with GMP standards. The theranostic potential was confirmed in experiments of treating the mammary adenocarcinoma with the MNP-HSA drug containing the immobilized doxorubicin (lifetime of animals suffering from mammary adenocarcinoma increased by 50%).
The photodynamic therapy (PDT) method is a promising approach to treating oncological diseases based on the use of organic molecules (photosensitizers) that, influenced by laser irradiation, produce free oxygen radicals that are toxic for tumor cells. The immobilization on the surface of MNP-HSA photosensitizer molecules allows obtaining MNPs with high activity in photodynamic therapy. In this case, the photosensitizer accumulation was assessed through the MRI method. which allows performing the PDT procedure in the optimal time compliant with the largest accumulation of the drug with the maximum efficiency. As exemplified by colon carcinoma with mice, we managed to achieve an accurate tumor reduction in 100% cases.
Magnetic hyperthermia is an experimental method of treating solid tumors thanks to the opportunity of injected magnetic nanoparticles to absorb energy of variable electromagnetic field and convert it to heat. Therefore, it becomes possible to ensure a local tumor heating up to the temperature above 42-43℃, which leads to the death of tumor cells. The heating efficiency is determined by a number of parameters, the key ones including the magnetizability and coercitive force of material, as well as the size and form of nanoparticles. At the first stage, we performed MNP screening in vitro in order to find MNPs with the highest distribution coefficient of electromagnetic energy absorption ensuring efficient heating. It was established that MNPs based on cobalt iron oxide (CoFe2O4) are prospective agents for magnetic hyperthermia. A high value of coercitive force allows regulating the tumor temperature with the accuracy of up to several degrees and effectively destroying tumor cells without affecting the healthy surrounding tissue. In vivo experiments on the colon cancer model with mice demonstrated that all mice exposed to magnetic hyperthermia demonstrated an accurate reduction in tumor growth, while 80% of animals made a complete recovery. Pre-clinical toxicity studies showed the absence of toxic effects with in vitro and in vivo tests.
Due to diversity of approaches to chemical modification, we managed to obtain stable water nanoparticle suspensions and to demonstrate their high efficiency as contrast MRI agents, drug delivery agents, as well as in tumor treatment by magnetic hyperthermia. The results were published in the leading peer-reviewed magazines: Journal of Controlled Release (IF= 7.877), Journal of Colloid and Interface Science (IF=6.361), Acta Biomaterialia (IF= 6.319), Nanomedicine: Nanotechnology, Biology, and Medicine (IF= 5.57), Colloids and Surfaces B: Biointerfaces (IF=3.973), Langmuir (IF=3.683), Journal of Biochemical and Molecular Toxicology (IF= 2.965), Journal of Magnetism and Magnetic Materials (IF= 2.683).
Scopus Hirsch Index — 13.
Number of articles on Scopus — 85.
ResearcherID O-5728-2017.
Scopus AuthorID 57202251748.
- Russian Foundation for Basic Research Grant No.
16-33 −60180 mol_а_dk “Hybrid materials based on iron oxide nanoparticles and derivative natural chlorophylls”,2016-2018; support amount — RUB 5,100,000; role — supervisor. - State Contract No. 14.N08.11.0059 “Pre-trial studies of contrast agent based on magnetic iron oxide nanoparticles for diagnostics of celebral tumors”,
2015-2017; support amount — RUB 44,000,000, role: principal investigator. - Grant of Russian President No. МК-6371.2016.7,
2016-2017; support amount — RUB 1,200,000; role — supervisor. - Grant of the Swedish Institute Nr 19806/2016 “INNOVIMMUNE: Baltic platform for the innovative immunotherapies”,
2017-2018; support amount: EUR 5,000; role — supervisor. - Russian Science Foundation Grant No. 17-74- 10169 “Magnetic iron oxide nanoparticles loaded with cisplatin in diagnostics and treatment of tumor diseases”, support amount: RUB 4,500,000; role — supervisor.
- Subsidy Agreement No. 14.575.21.0147 “Developing the technology of personalized assessment and prediction of the efficiency of delivering nanoformulations of antitumor drugs with the use of a complex of intravital reaearch methods”, support amount: RUB 60,000,000; role — principal investigator.
- Intravital imaging of liposome behavior upon repeated administration: A step towards the development of liposomal companion diagnostic for cancer nanotherapy Journal of Controlled Release, 2021, 330, стр.
244-256. - Temperature-controlled magnetic nanoparticles hyperthermia inhibits primary tumor growth and metastases dissemination Nanomedicine: Nanotechnology, Biology, and Medicine, 2020, 25, 102171.
- Extravasating Neutrophils Open Vascular Barrier and Improve Liposomes Delivery to Tumors ACS Nano, 2019, 13(11), стр.
12599-12612. - Intravital microscopy reveals a novel mechanism of nanoparticles excretion in kidney Journal of Controlled Release, 2019, 307, стр.
368-378. - Synthesis and characterization of bacteriochlorin loaded magnetic nanoparticles (MNP) for personalized MRI guided photosensitizers delivery to tumor Journal of Colloid and Interface Science, 2019, 537, стр.
132-141. - Toxicity of iron oxide nanoparticles: Size and coating effects Journal of Biochemical and Molecular Toxicology, 2018, 32(12), e22225.
- Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer Nanomedicine: Nanotechnology, Biology, and Medicine, 2018, 14(5), стр.
1733-1742. - VEGF-targeted magnetic nanoparticles for MRI visualization of brain tumor Nanomedicine: Nanotechnology, Biology, and Medicine, 2015, 11(4), стр.
825-833. - Core-shell-corona doxorubicin-loaded superparamagnetic Fe3O4 nanoparticles for cancer theranostics Colloids and Surfaces B: Biointerfaces, 2015, 136, стр.
1073-1080.
- 2723894 (18.06.2020). Method of obtaining a drug for diagnostics of neoformations through the use of magnetic resonance imaging.
- 2530762 (10.10.2014). Method of diagnosing multiform glioblastoma with the use of MRI.
- 2659949 (04.07.2018). Method of obtaining a drug based on iron oxide magnetic nanoparticles (MNP) for MRI diagnostics of neoformations.
- 2657545 (14.06.2018). Drug for treating mammary cancer.
- 2723932 (18.06.2020). Drug for diagnostics of neoformations through the use of magnetic resonance imaging.
- 2712212 (27.01.2020). Method of treating oncological diseases through drug injections.
- 2657835 (15.06.2018). Method of obtaining a system to deliver an antitumor drug into tumor cells.
- 2664062 (14.08.2018). Method of obtaining clusters of magnetite nanoparticles.
- Expert opinion: commentary of MISIS scientists to the future of medical professions (Nauchnaya Rossiya)
- Like a key to the lock. A new method of drug delivery will increase their efficiency manyfold (Poisk newspaper)
- A Russian drug has increased the life of mice suffering from cancer by a record-breaking period (RIA Novosti)
- “Light killers” along with magnetic nanoparticles have been tested for cancer treatment (Indicator)
- Force of light: Russian scientists have created a new cancer treatment method (Izvestia)