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Contract number
14.Z50.31.0022
Time span of the project
2014-2018

As of 15.02.2021

24
Number of staff members
112
scientific publications
12
Objects of intellectual property
General information
Name of the project: Biocompatible luminescent nanocomplexes for theranostics

Strategy for Scientific and Technological Development Priority Level: в

Goals and objectives
Research directions:

  • Creating new generation multifunctional theranostic agents based on luminescent inorganic nanomaterials
  • Developing cell and animal models for in vivo testing of created agents
  • Creating of instruments ensuring high sensitivity registering of developed agents for optical bioimaging of cells and tissues

Project objective:

Developing complex approaches for efficient diagnostics and therapy of pathologies including: multifunctional new generation theranostic based on luminescent inorganic nanomaterials, call and animal models for in vivo testing of created agents, equipment providing high sensitivity registering of various agents for optical bioimaging of cells and tissues

The practical value of the study

New generation multifunctional theranostic antitumor agents based on organic and inorganic materials, which allow targeted labeling and visualization of tumor cells and selectively affect them without affecting normaltissueshave been developed. Cellular and animal models were developed for in vivo testing of the abovementioned theranostic agents, in particular, a fluorescent tumor model was created for in vivo evaluation of the effectiveness of antitumor agents.Highly sensitive instruments for registration of theranostic agents based on organic and inorganic materials for optical bioimaging of cells and tissues have been developed and tested. New compounds of porphyrazine nature based on cyanoporphyrazine chromophores and their metal complexes, including the gadolinium porphyrazine complex, were obtained. An instrument base and an appropriate approach has been developed to evaluate the photodynamic efficiency of photosensitizers in vitro and in vivo.

Implemented results of research:

1. License Agreement No. 02-13 / 01L dated 13.02.2017. between the Lobachevsky National Research University and "BioIntegrator"LLC.The contract is valid for 10 years: from 13.02.2017 to 13.02.2027. The amount of the deal is0 rubles.

Brief description of the field of use: manufacture, application, offer for sale, sale, other introduction into civil circulation on the territory, storage for these purposes of products under license of a drug based on a recombinant protein toxin specific to cells expressing the HER2 receptor for preclinical, clinical studies and treatment of tumors characterized by increased expression of the HER2 receptor.

2. License Agreement no. L-1/17 dated 27.02.2017. Between the Lobachevsky National Research University and "STC Amplituda"LLC. Valid for 2 years: from 27.02.2017 to 27.02.2019. The amount of the deal is 200,000 rubles.

Brief description of the field of application: analysis of images of biological samples labeled with phosphorescent nanomaterials, or samples of phosphorescent nanomaterials deposited on glass to determine the localization of discrete phosphorescent particles and the photoluminescence lifetime of each of them.

3. License Agreement No. 942 dated 29.03.2017. Between the Lobachevsky National Research University and "STC Amplituda" LLC.Valid for 2 years: from 29.03.2017 to 29.03.2019.The amount of the deal is 400,000 rubles.

Brief description of the field of use: A drug consisting of a transport module and a cytotoxic component specific to cells expressing the HER2 receptor for preclinical and clinical studies of tumor diseases characterized by increased expression of the HER2 receptor.

4. License Agreement no. L-14/18 dated 09.08.2018. Between the Lobachevsky National Research University and "STC Amplituda"LLC. Valid for 2 years: from 09.08.2018 to 09.08.2020. The amount of the deal is 400,000 rubles.

Brief description of the field of use: application for research purposes for preclinical and clinical trials of the method of microscopic examination of biological samples marked with phosphorescent probes in vitro.

5. License agreement No. L-18 / 19ot 13.12.2019. Between the Lobachevsky National ResearchUniversity and “SLC”LLC. Valid for 1 year: from 13.12.2019 to 13.12.2020. The amount of the deal is 50,000 rubles.

Brief description of the field of use: application for research purposes for preclinical, clinical trials to determine the technical characteristics of optical irradiation sources for medical and research purposes.

Education and career development:

  • New educational courses, programs developed in the laboratory:

- "Biophotonics" for“Bioinformatics”Master's program (2020)

- "Methods of bioimaging" for the training of specialists studying in the programs “Medical Biophysics”, “Medical Biochemistry”, “Medical Cybernetics” (2019);

- "Physics, Medical Physics" for the training of specialists studying in the “Dentistry” and “Medical Science” programs (2019)

- "Medical Biophysics" for training specialists studying in "Medical Biophysics"program (2018)

- “Special Chapters of Physical and Chemical Sciences”for the training ofundergraduates studying in "Biology" program (2017)

- “Nanobiophotonics”for the training ofthe 1st year undergraduates in "Biology" program (2016).

- “Optical theranostics”. Postgraduate Training Program (2015)

- “Methods of bioimaging”. Bachelor's Degree Program (2015)

- “Biocompatible photoluminescent nanocomplexes for theranostics”. Professional Development Program (2015)

  • Graduated: 6 PhDs, 2 Doctors of Science.

  • The members of the research team have completed the following advanced training courses:

- Academic English, 72 h, UNN (2019)

- Important trends in the development of professional biological and ecological education: the implementation in practice IBBM, 250 hours, UNN (2019)

- Radiation safety and radiation control (2019, 2015)

- Implementation of the model testing of the basic principles of continuous medical education (2018)

- Seminar on electrophoresis and blotting (2017)

- Master class on fluorescence spectroscopy (2017)

- Internship in the "Remote controlled theranostic systems"laboratory on the topic: "Catheterization of the carotid artery, injection in the femoral artery of mice, preparation of cryogenic samples and general cryotome utilization, the biochemical basis of preparation and fixation of histological preparations" (2016)

- 1st schoolon ADFLIM (2016)

- Training of thepressure vesselservice personnel (2020, 2019, 2018, 2017, 2016, 2015);

- Merck Millipore Life Science Day (2015)

- FPLC: classic technology in a modern format (2015)

- Theoretical and practical fundamentals and rules of operation of the analyzer Zetasizer Nano (2015)

- Protein Purification and Separation School (2015)

- BIOSYNTHESIS: an international study for biology and biomedicine (2015)

- Gestion des ressources humaines dans les universités françaises(2015)

- Functional flow cytometry in scientific and clinical research. Practical application of the method (2015)

- Distance Education Technologies (2015)

- Young Teacher's School (2015)

- "Modern methods of Experimental Biophysics" summer school (2014).

  • Members of the research team took part in the following conferences:

- 24th, 23rd, 22nd, 21st, 20th, 19th International Pushchino School-Conference of Young Scientists "Biology-Science of the XXI Century", 2020, 2019, 2018, 2017, 2016, 2015 yy.

- VIIth Youth School-Conference on Molecular and Cell Biology of the Institute of Cytology of the Russian Academy of Sciences, 2020

- VIIth Troitsk Conference with International Participation "Medical Physics" (TCFM-7), 2020

- 27th Annual Conference of Society for Redox Biology & Medicine, 2019

- VIth All-Russian Conference of Young Scientists and Students with International Participation VOLGAMEDSCIENCE, 2019

- 74th, 73d, 72nd, 71st, 70th, 69th, 68th, 67th All-Russian with international participation School-Conference of young scientists "Biology: organization, behavior, management".(2021,2020,2019,2018, 2017, 2016, 2015, 2014)

- Regional conference of young scientists FUNDAMENTAL SCIENCE FOR MEDICINE (FSM-2019),Nizhniy Novgorod, Russia, 2019

- VIIth International Symposium “Topical Problems of Biophotonics 2019”, 2019

- VIth Congress of Biophysicists of Russia, 2019

- «Patient-tailored biomaterials for tissue regeneration combating microbial contamination and drug delivery»workshop, 2019

- XIIIth International Scientific Conference “Topical Issues of Biological Physics and Chemistry”, Sevastopol, 2018

- Vth International Conference “POSTGENOME 2018", Kazan, 2018

- International Scientific Conference of Students, Postgraduates and Young Scientists "Lomonosov -2017", Moscow, 2017

- International Conference "Receptors and Intracellular signaling", Pushchino, 2017

- VIth All-Russian School-Conference of Young Scientists "Organic and Hybrid Nanomaterials", Ivanovo, 2017.

- VIth International Symposium "Topical Problems of Biophotonics 2017", 2017

- Xth All-Russian with international participation Congress of Young Biologists “Symbiosis 2017”, Kazan, 2017

- 1st International School Conference for Young scientists “Smart nanosystems fortranslation medicine”, St. Petersburg, 2017

- International Scientific Conference of Students, Postgraduates and Young Scientists "Lomonosov -2016", Moscow, 2016

- All-Russian Forum «Science of the future», Kazan, 2016

- International Symposium Optics and Biophotonics, Saratov, 2016

- Vth Congress of Biochemists of Russia, Dagomys, 2016

- “OpenScienсe” Youth Scientific Forum, Moscow, 2016

- "Proteins and Peptides"Symposium, Novosibirsk, 2015

- VthInternational Symposium “Topical Problems of Biophotonics 2015”, 2015

- 16th Congress of the European Society for Photobiology, Portugal, 2015

- Vth Congress of Biophysicists of Russia, Rostov-on-Don, 2015

- Conference "Science of the Future", St. Petersburg, 2014

- VIIth Congress of the Russian Photobiological Society, Shepsi, Krasnodar Territory, 2014

- International Scientific Conference on Bioorganic Chemistry, Biotechnology and Bionanotechnology, dedicated to the 55th anniversary of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the RAS and the 80th birthday of the Academician Yu. A. Ovchinnikov, Moscow, 2014

- Seminar of the Department of Biophysics and Biotechnology of the Faculty of Biology of VSU, Voronezh, 2014

  • All-Russian with international participation school-conference of young scientists "Biosystems: Organization, Behavior, Management" is annually organized on the basis of the Lobachevsky National Research University, Nizhny Novgorod.

Organizational and structural changes:

Since 2015, the Laboratory of Optical Theranostics has become a part of the Biophysics Research Center of the Institute of Biology and Biomedicine of the Lobachevsky National Research University.

Collaborations:

  • Macquarie University (Australia): collaborative research, collaborative training сollaborative publications, сollaborative research projects:

- Contract for the research work No. 54-14-EP dated 06.10.2014 on the topic "Development of a method for ultra-sensitive optical imaging for the visualization of nanoparticles by the deferred registration method".

- Contract for the research work No. 153-15-EP dated 06.11.2015on the topic "Adaptation of the whole-body fluorescent imagingmethod for the detection of up-conversion nanophosphores".

- Collaborative supervision agreement for Doctoral research of Rozova V. S. by Macquarie University and Lobachevsky National University.

  • Jilin University (China): сollaborative research.

- International cooperation agreement for the implementation of the project on the topic "Biofunctional theranostic nanocomplexes for the combined therapy of oncological diseases" (code TherNC). (BRICS Multilateral Research Initiative). Project cooperation agreement no. b/n dated 08.11.2017.

-The project of the Federal Target Program "Research and development in priority areas of development of the scientific and technological complex of Russia for 2014-2020". Agreement on the provision of a grant from the federal budget in the form of a subsidy No. 075-02-2018-216 dated 26.11.2018, No. 075-15-2019-953 "31" May 2019.

  • University of Delhi (India): сollaborative research.

- International cooperation agreement for the implementation of the project on the topic "Biofunctional theranostic nanocomplexes for the combined therapy of oncological diseases" (code TherNC). (BRICS Multilateral Research Initiative). Project cooperation agreement no. b/n dated 08.11.2017.

- The project of the Federal Target Program "Research and development in priority areas of development of the scientific and technological complex of Russia for 2014-2020". Agreement on the provision of a grant from the federal budget in the form of a subsidy No. 075-02-2018-216 dated 26.11.2018, No. 075-15-2019-953 "31" May 2019.

  • Ghent University (Belgium): сollaborative research, сollaborative publications.
  • Fudan University (China): сollaborative research.

RFBR project (type GFEN_a). Competition for the best scientific projects of basic research, held collaboratively by the federal state budgetary institution "Russian Foundation for Basic Research" and the State Foundation of Natural Sciences of China. Contract No. 19-54-53025 on the topic "Combination of luminescent IR imaging and MR imaging for real-time tracking of stem cells".

  • Shemyakin-Ovchinnikov Institute of bioorganic chemistry of the Russian Academy of Sciences (Russia): сollaborative research, сollaborative publications.

Collaborative project of the RSF (2019 Competition for the event "Conducting research on the basis of the existing world-class scientific infrastructure" of the Presidential Program of Research Projects implemented by leading scientists, including young scientists) Agreement No. 19-74-20168 of 17.04.2017.

  • Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences (Russia): сollaborative research, сollaborative publications, сollaborative research projects:

- Agreement No. 57-17-EP dated 26.06.2017 on the topic "Synthesis of the tetra(aryl) series)tetracyanoporphyrazines with various aryl substituents».

- Agreement No. 52-18-EP dated 05.05.2018 on the topic "Synthesis of tetra (aryl)tetracyanoporphyrazines and analysis of their properties on model media and human cell cultures».

- Agreement No. 63-19-EP of 29.08.2019 on the topic "Synthesis of photodynamic dyes of the tetra(aryl) series)tetracyanoporphyrazines and analysis of their photophysical properties».

  • Institute of Applied Physics of the Russian Academy of Sciences (N. Novgorod, Russia): сollaborative research, сollaborative publications, сollaborative research projects:

- Contract No. 63-17-EP of 18.07.2017 on the topic " Study of the lifetime of the excited state of porphyrazine chromophores in animal tissues during the development of a response to photodynamic exposure»

- Agreement No. 6-18-EP of 05.02.2018.

- Agreement No. 39-19-EP of 29.04.2019.

  • Privolzhsky Research Medical University (Russia): сollaborative research, сollaborative publications.

  • Federal research center "Crystallography and photonics" of the Russian Academy of Sciences (Russia): сollaborative research, сollaborative publications, сollaborative research projects:

- Contract No. 93-15-EP dated 14.07.2015 on the topic "Development of an optical tomographic system for the visualization of pathologically altered tissues marked with luminescent nanocomplexes in small animals».

- Contract No. CCP.17.18 dated 16.10.2017 on the topic "Obtaining microphotographs of NaYF4 nanoparticles by transmission electron microscopy".

  • I.M. Sechenov First Moscow State Medical University (Russia): сollaborative research, сollaborative publications, сollaborative research projects:

- Contract No. 2439-d dated 25.12.2019 on the topic "Development of an approach to the delivery of antitumor agents using submicron containers».

- Agreement No. 1808-d of 26.10.2020 on the topic "Creation of targeted biohybrid nanoconstructions based on infrared dyes».

- Contract No. 1809-d of 26.10.2020 on the topic "Research of diagnostic and therapeutic properties of biohybrid nanostructures in vivo».

  • "STC Amplituda" LLC (Russia): сollaborative research.

-International cooperation agreement for the implementation of the project on the topic "Biofunctional theranostic nanocomplexes for the combined therapy of oncological diseases" (code TherNC). (BRICS Multilateral Research Initiative). Project cooperation agreement no. b/n dated 08.11.2017.

- The project of the Federal Target Program "Research and development in priority areas of development of the scientific and technological complex of Russia for 2014-2020". Agreement on the provision of a grant from the federal budget in the form of a subsidy No. 075-02-2018-216 dated 26.11.2018, No. 075-15-2019-953 "31" May 2019.

  • G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences (Russia): сollaborative research project on the topic: "Expression and purification of recombinant proteins ORF8, ORF10, and ORF3a".

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Alzeibak R., Mishchenko T.A., Shilyagina N.Y., Balalaeva I.V., Vedunova M.V., Krysko D.V.
Targeting immunogenic cancer cell death by photodynamic therapy: Past, present and future / Journal for ImmunoTherapy of Cancer. 2021. V. 9, I. 1, № e001926. IF 10.252doi:10.1136/jitc-2020-001926
Sokolova E.A., Vodeneev V.A., Deyev S.M., Balalaeva I.V.
3D in vitro models of tumors expressing EGFR family receptors: a potent tool for studying receptor biology and targeted drug development / Drug Discovery Today. 2019. V. 24, I. 1, P. 99-111. IF 7.321 doi:10.1016/j.drudis.2018.09.003
Kutova, O.M., Guryev, E.L., Sokolova, E.A., Alzeibak, R., Balalaeva, I.V.
Targeted delivery to tumors: Multidirectional strategies to improve treatment efficiency / Cancers. 2019. V. 11, I. 1, № 68 IF 6.126 doi:10.3390/cancers11010068
Guryev E.L., Shilyagina N.Y., Kostyuk A.B., Sencha L.M., Balalaeva I.V., Vodeneev V.A., Kutova O.M., Lyubeshkin A.V., Yakubovskaya R.I., Pankratov A.A., Ingel F.I., Novik T.S., Deyev S.M., Ermilov S.A., Zvyagin A.V.
Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles / Toxicological Sciences. 2019. V. 170, I. 1, P. 123-132 IF 3.564 doi:10.1093/toxsci/kfz086
Alexey B. Kostyuk, Artem D. Vorotnov, Andrey V. Ivanov, Arthur B. Volovetskiy, Aleksandr V. Kruglov, Lyudmila M. Sencha, Liuen Liang, Evgenii L. Guryev, Vladimir A. Vodeneev, Sergey M. Deyev, Yiqing Lu, Andrei V. Zvyagin
Resolution and contrast enhancement of laser-scanning multiphoton microscopy using thulium-doped upconversion nanoparticles / Nano Research, 2019, 12, 2933–2940. IF 8.515 doi:10.1007/s12274-019-2527-0
Gudkov, S.V., Guryev, E.L., Gapeyev, A.B., Bruskov, V.I., Zvyagin, A.V.
Unmodified hydrated С60 fullerene molecules exhibit antioxidant properties, prevent damage to DNA and proteins induced by reactive oxygen species and protect mice against injuries caused by radiation-induced oxidative stress / Nanomedicine: Nanotechnology, Biology, and Medicine. 2019. V 15(1), P. 37–46. IF 5.803 doi: 10.1016/j.nano.2018.09.001
Guryev, E.L., Volodina, N.O., Shilyagina, N.Y., Gudkov, S.V., Balalaeva, I.V., Volovetskiy, A.B., Lyubeshkin, A.V., Sen, A.V., Ermilov, S.A., Vodeneev, V.A., Petrov, R.V., Zvyagin, A.V., Alferov, Z.I., Deyev, S.M.
Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer / Proceedings of the National Academy of Sciences of the United States of America. 2018. V. 115, I. 39, P. 9690-9695. IF 9.504 doi:10.1073/pnas.1809258115
Liang L.U., Lu YQ., Zhang R., Care A.,Ortega T.A., Deyev S.M., Qian Y., Zvyagin A.V.
Deep penetrating photodynamic therapy with KillerRed mediated by upconversion nanoparticles / ACTA BIOMATERIALIA. 2017.V.51, P. 461-470. IF 7.502doi: 10.1016/j.actbio.2017.01.004
Sokolova E., Proshkina G., Kutova O., Shilova O., Ryabova A., Schulga A., Stremovskiy O., Zdobnova T., Balalaeva I., Deyev S.
Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo / Journal of Controlled Release. 2016. V. 233, P. 48-56. IF 7.727 doi:10.1016/j.jconrel.2016.05.020
Gudkov S.V., Shilyagina N.Y., Vodeneev V.A., Zvyagin A.V.
Targeted radionuclide therapy of human tumors / International Journal of Molecular Sciences. 2015. V. 17, I. 1, № 33. IF 4.653 doi: 10.3390/ijms17010033
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