The main competitive advantages and professional competencies of LOX employees lie in the development of nanohybrid systems for use in medical diagnostics and optoelectronics. Having been established in 2011, based on a mega-grant received by Professor Igor Nabiev within the framework of the program of attracting leading scientists to Russian institutions of higher special education, the group is recognized as one of the most successful “Mega-grant” structures that continue to function effectively under the leadership of its leading scientist.
LOX staff were the first European scientists in the field of synthesis of fluorescent tags based on quantum dots (QDs) and their application in medicine [1, 2]. The created suspension chips for flow cytometry based on polymer microspheres encoded by QDs, as well as nanoprobes based on conjugates of single-domain antibodies (odATs) and QDs allow successful detection of serological and histological oncomarkers, such as CEA [3,4], HER2 [5], prostate-specific antigen PSA [6], as well as multiparametric serological detection of lung cancer oncomarkers [7]. The sensitivity of the obtained CT-based probes is so high that it allows the detection of individual cancer cells and micrometastases [8]. Application of the procedure of oriented conjugation of odAt and CT allows to create ultra-compact probes that easily penetrate tumor tissues and allow obtaining three-dimensional images [9-11]. CTs are also suitable for use in theranostic systems, providing controlled drug delivery to tumor tissues [12-14].

Among the main scientific results of the LOX staff in recent years, the following should be noted:

1. A unique setup for realization of the strong light-substance coupling mode for a wide class of compounds, including biological molecules and complexes, was created, patented and described:
NABIEV, I.R., MOCHALOV, K.E., RAKOVICH, Y.P., SOKOLOV, P.M., DOVZHENKO, D.S., MEZIN, A.V. Method of modifying the properties of sample molecules and a device for its realization. Invention. Patent of the Russian Federation No. 2666853. Registered in the State Register of Inventions of the Russian Federation 12.09.2018.
Mochalov, K.E., Vaskan, I.S., Dovzhenko, D.S., Rakovich, Yu.P., NABIEV, I.R.. (2018) A versatile tunable microcavity for investigation of light-matter interaction. Review of Scientific Instruments. 89, 053105

2. High toxicity of nanoparticles for living organisms is a factor limiting their in vivo applications. The LOCS team systematized and analyzed the mechanisms of nanoparticle toxicity to living systems and concluded which physical and chemical properties of nanoparticles have the greatest influence on their toxicity.
The article describing these results has been cited more than 820 times.
SUKHANOVA, A., Bozrova, S., SOKOLOV P., Berestovoy, M., Karaulov, A., NABIEV, I. (2018) Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties. Nanoscale Research Letters, 13, 44 (2018). Impact factor (IF) = 5.418. Q1. DOI: 10.1186/s11671-018-2457-x

3. A solar cell based on the hybrid material quantum dots – bacteriorhodopsin was created and the possibility of significantly enhancing the solar energy conversion efficiency by utilizing quantum dots under two-photon excitation was demonstrated.
Biosensors and Bioelectronics, 137, 117-122 (2019). IF = 10.618. DOI: 10.1016/j.bios.2019.05.009

4. Possible applications of the induced transparency effect in hybrid plasmon-exciton structures for sensing applications are described.
Laser & Photonics Reviews, 13, 1800176 (2018). IF = 13.138. DOI: 10.1002/lpor.201800176.

5. The double Rabi splitting effect in a system with strong light-matter coupling based on Au/Ag core/shell nanorods and J-aggregates of several fluorophores is detected and characterized.
The Journal of Physical Chemistry Letters, 10, 6137-6143 (2019). IF = 6.888. DOI: 10.1021/acs.jpclett.9b01988

6. Enhanced biexiton emission resulting from long-range interaction between single quantum dots and gold nanorods in thin-film hybrid nanostructures is demonstrated for the first time.
The Journal of Physical Chemistry Letters, 10, 481-486 (2019). IF = 6.888. DOI: 10.1021/acs.jpclett.8b03549

7. Possible system configurations, realization conditions, and possible applications of the light-matter interaction effect in the strong coupling regime are described.
Nanoscale, 10, 3589-3605 (2018). IF = 8.307. DOI: 10.1039/C7NR06917K

8. We demonstrate the ability to create microcapsules encoded by fluorescent and magnetic nanocrystals with controlled energy transfer to the surrounding polymers, which provides suppression of “‘flicker’” fluorescence of the capsules and expands their use as drug delivery vehicles.
ACS Applied Materials and Interfaces, 12 (32), 35882-35894 (2020). IF=10.383. DOI: 10.1021/acsami.0c08715

9. A device that enables multiparameter detection of multiple oncomarkers by recording changes in surface modes of photonic crystals is constructed and described, and its applications are demonstrated.
Scientific Reports, 9, 8745 (2019). DOI: 10.1038/s41598-019-45166-3

10. The ability to detect DNA-PKcs kinase enzyme activity using a quantum dot-based microarray is demonstrated.
Scientific Reports, 8, 10968 (2018). DOI: 10.1038/s41598-018-29256-2

11. We show for the first time that human micrometastases and disseminated cancer cells can be visualized in one-photon and two-photon modes, using conjugates of nano-bodies and quantum dots.
Scientific Reports, 8, 4595 (2018). DOI: 10.1038/s41598-018-22973-8

12 We describe (1) the basic principles of designing multilayer capsules – drug delivery systems – specific to cancer cells, (2) analyze the effects of interactions of capsules with cellular and molecular components of biological fluids, and (3) present the key structural parameters that determine the efficiency of the targeted action of capsules on cancer cells. Fundamental structural and functional principles determining future directions for the development of theranostic systems based on multilayer capsules are formulated.
Biomaterials Science, 7, 44668 (2022). https://doi.org/10.1039/D2BM00829G IF = 7.59. DOI: 10.1039/D2BM00829G

13. A method for determining the single-exciton two-photon absorption cross section of semiconductor nanocrystals by measuring the saturation of their photoluminescence under two-photon excitation has been developed.
ACS Photonics, 7 (3), p. 831-836. IF=7.529. DOI: 10.1021/acsphotonics.9b01820

14. A patent for a useful model of a flow cell for chemical reactions in the strong coupling mode has been obtained: SOKOLOV P.M., DOVZHENKO D.S., SAMOKHVALOV P.S., NABIEV I.R. Flow cell for chemical reactions. Useful model. Patent Application No. 2019133026/28. Date of filing: 18.10.2019. Date of decision on granting the patent: 27.11.2019.

15. Patent registered for a set for differential diagnosis of diseases : NABIEV I.R., SUKHANOVA A.V., Tkachuk A.P., SOKOLOV P.M. Set for differential diagnosis of diseases. Invention. Patent of the Russian Federation No. 2701742. Registered in the State Register of Inventions of the Russian Federation on 01.10.2019. https://findpatent.ru/patent/270/2701742.html

The main project currently being implemented by the LOX laboratory at the LIFT Center is the Q-LIGHT project, which should provide a synergy between the use of innovative fluorescent nanoprobes for the detection of oncomarkers of lung cancer and breast cancer with radiation detectors optimized to work with the nanoprobes being created, which will lead to the creation of integrated diagnostic systems based on optical quantum biosensors, providing at least an order of magnitude higher sensitivity of molecular diagnostics of lung cancer and breast cancer.

References

1. SUKHANOVA, A., Venteo, L., Devi, J., Artemiev, M., Oleynikov, V., Pluot, M., and NABIEV, I. (2002) Highly stable fluorescent nanocrystals as a new class of tags for immunohistochemical analysis of paraffin-embedded tissue sections. Laboratory Research, 82, 1259-1262.

2. SUKHANOVA, A., Dewi, J., Venteo, L., Kaplan, H., Artemyev, A., Oleynikov, V., Klinov, D., Pluot, M., Cohen, J.H.M., NABIEV, I. (2004) Biocompatible fluorescent nanocrystals for immunolabeling of membrane proteins and cells. Analytical Biochemistry, 324, 60-67.

3. SUKANOVA, A. et al. Oriented conjugates of single-domain antibodies and quantum dots: Toward a new generation of ultra-small diagnostic nanoprobes // Nanomedicine: Nanotechnology, Biology and Medicine. 2012, Vol. 8, P. 516-525.

4. Rakovich T. Ya. et al. Highly sensitive single-domain antibody-quantum dot conjugates for detection of low levels of HER2 biomarker expression in lung and breast cancer cells // ACS Nano. 2014, Vol. 8, P. 5682-5695.

5. Brazhnik K. et al. Quantum dot-based lab-on-a-bead system for multiplexed detection of free and total prostate-specific antigens in clinical human serum samples // Nanomedicine: Nanotechnology, Biology, and Medicine. 2015, Vol. 11, P. 1065-1075.

6. Bilan R. et al. Quantum dot-based suspension microarray for multiplexed detection of lung cancer markers: preclinical validation and comparison with Luminex xMAP® system // Scientific Reports. 2017, Vol. 7, 44668.

7. Ramos-Gomes F. et al. Single- and two-photon imaging of micrometastases and disseminated human tumor cells using conjugates of nanobodies and quantum dots // Scientific Reports. 2018, Vol. 8, 4595.

8. Brazhnik K., Nabiev I., Sukhanova A. Oriented conjugation of single-domain antibodies and quantum dots // Quantum Dots: Applications in Biology. Humana Press, New York, NY, 2014, P. 129-140.

9. Brazhnik K., Nabiev I., Sukhanova A. Improved procedure of oriented conjugation of full-length antibodies with quantum dots // Quantum Dots: Applications in Biology. Humana Press, New York, NY, 2014, P. 55-66.

10. Mochalov K. E. et al. Instrumental approach to combining confocal microspectroscopy and 3D scanning probe nanotomography // Ultramicroscopy. 2017, Vol. 182, P. 118-123.

11. Nifontova G. et al. Nanoparticle-doped hybrid polyelectrolyte microcapsules with controlled photoluminescence for potential bioimaging applications // Polymers. 2021, Vol. 13, No. 23, 4076.

12. Nifontova G. et al. Cancer cell targeting with functionalized quantum dot-encoded polyelectrolyte microcapsules // Frontiers in Chemistry. 2019, Vol. 7, 34.

13. Nifontova G. et al. Bioimaging tools based on polyelectrolyte microcapsules encoded with fluorescent semiconductor nanoparticles: Design and characterization of the fluorescent properties // Nanoscale Research Letters. 2019, Vol. 14, 29.

14. Nifontova G. et al. Next-generation theranostic agents based on polyelectrolyte microcapsules encoded with semiconductor nanocrystals: development and functional characterization // Nanoscale Research Letters. 2018, Vol. 13, 30.