2016, Sizova, S. V., Oleinikov, V. A., Bouchonville, N., Molinari, M., Samokhvalov, P. S., Sukhanova, A., Nabiev, I., Суханова, Алена Владимировна, Набиев, Игорь Руфаилович, Олейников, Владимир Александрович

The integration of novel nanomaterials with highly functional biological molecules has numerous advanced applications, including optoelectronics, biosensing, imaging, and energy harvesting. This review summarizes recent progress in understanding the mechanisms of energy transfer between semiconductor nanocrystal (so-called quantum dots [QDs]) and photosensitive proteins in heterostructures, such as hybrids of semiconductor nanocrystals with purple membranes containing bacteriorhodopsin (bR) or with photosynthetic reaction centers (RCs). Understanding of these mechanisms should enable prediction of the possible ways to improve the biological function of biomolecules by means of their assembling with QDs and develop novel functional materials with controlled photonic properties and applications. The possible mechanisms of energy transfer from QDs to photochromic biomolecules are discussed and correlated with experimental data. The principles of hybrid structures engineering, donor/acceptor parameters affecting both energy transfer efficiency and biological function, and functionality of these hybrid structures are described. New nanobiohybrid materials are shown to have advanced implications for optoelectronics, photonics, and photovoltaics due to the ability of nanocomponents of these materials for efficient energy harvesting, conversion, and transfer of additional energy to Biosystems, thus making them working more efficiently.

2021, Sukhanova, A., Mochalov, K., Samokhvalov, P., Nifontova, G., Tsoi, T., Nabiev, I., Самохвалов, Павел Сергеевич, Нифонтова, Галина Олеговна, Цой, Татьяна Дмитриевна, Набиев, Игорь Руфаилович

© 2021 Institute of Physics Publishing. All rights reserved.Fast, sensitive, high-throughput detection of coronavirus antigens at physiologically relevant levels is essential for population screening that could prevent epidemics such as the current COVID-19 global pandemic. Optical methods based on surface-enhanced Raman scattering (SERS) spectroscopy are promising for this purpose because they ensure quick detection of even single biological molecules in a sample. For achieving such a high sensitivity, it is crucial to design SERS-active systems concentrating incident radiation into small sample volumes. Here, metal-dielectric cavities have been obtained through interaction of protein sulfhydryl groups with a SERS-active silver surface. The concentration of light in these cavities allows the differential detection of spike glycoprotein and nucleocapsid protein of SARS-COV-2, which are its key antigens, at physiologically relevant concentrations. The cavity Q-factor can be increased by additionally covering the dielectric protein film with a silver shell to form an ultrathin cavity, which provides an at least tenfold enhancement of the detection signal. The results could be used to design high-throughput systems for specific and sensitive detection of viral antigens and quick diagnosis of viral infections.

2022, Sarychev, A. K., Sukhanova, A., Ivanov, A. V., Bykov, I. V., Bakholdin, N. V., Vasina, D. V., Gushchin, V. A., Tkachuk, A. P., Nifontova, G., Samokhvalov, P. S., Karaulov, A., Nabiev, I., Нифонтова, Галина Олеговна, Самохвалов, Павел Сергеевич, Набиев, Игорь Руфаилович

Surface-enhanced Raman scattering (SERS) spectroscopy is a surface-or cavity-enhanced variant of Raman scattering spectroscopy that allows the detection of analytes with a sensitivity down to single molecules. This method involves the use of SERS-active surfaces or cavities capable of concentrating incident radiation into small mode volumes containing the analyte. Here, we have engineered an ultranarrow metal–dielectric nano-cavity out of a film of the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) glycoprotein and a silver surface, held together by interaction between reduced protein sulfhydryl groups and silver. The concentration of light in this nano-cavity allows the label-free recording of the characteristic Raman spectra of protein samples smaller than 1 pg. This is sufficient for the ultrasensitive detection of viral protein antigens at physiologically relevant levels. Moreover, the protein SERS signal can be increased by several orders of magnitude by coating the RBD film with a nanometer-thick silver shell, thereby raising the cavity Q-factor. This ensures a sub-femtogram sensitivity of the viral antigen detection. A simple theoretical model ex-plaining the observed additional enhancement of the SERS signal from the silver-coated protein is proposed. Our study is the first to obtain the characteristic Raman and SERS spectra of the RBD of S glycoprotein, the key SARS-CoV-2 viral antigen, directly, without the use of Raman-reporter mol-ecules. Thus, our approach allows label-free recording of the characteristic spectra of viral antigens at concentrations orders of magnitude lower than those required for detecting the whole virus in biological media. This makes it possible to develop a high-performance optical detection method and conformational analysis of the pathogen and its variants. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

2019, Ramos-Gomes, F., Chames, P., Baty, D., Alves, F., Sukhanova, A., Samokhvalov, P., Nabiev, I., Суханова, Алена Владимировна, Самохвалов, Павел Сергеевич, Набиев, Игорь Руфаилович

© 2019 SPIE.Semiconductor quantum dots (QDs) are characterized by orders of magnitude higher multiphoton linear absorption cross-sections compared with conventional organic dyes. Combined with the QD photoluminescence quantum yield approaching 100%, this fact opens great prospects for the twophoton functional tumor imaging with QDs tagged with highly specific recognition molecules. Single-domain antibodies (sdAbs) or "nanobodies" derived from lamas are the smallest high-affinity recognition molecules, which may be tagged with the QDs thus permitting not only solid tumors multiphoton imaging but also rare disseminated cancer cells and micrometastases in the depth of the tissue to be detected. Additionally, unique photostability of QDs enables signal accumulation and significant enhancement of the sensitivity of routine biochemical and immunohistochemical assays to be obtained when the conjugates of QDs, instead of organic dyes, are used.

2021, Sukhanova, A., Kalenichenko, D., Nifontova, G., Nabiev, I., Калениченко, Дарья Владимировна, Нифонтова, Галина Олеговна, Набиев, Игорь Руфаилович

© 2021 Institute of Physics Publishing. All rights reserved.The development of delivery systems providing prolonged release of antitumor drugs represents one of the challenges in designing and optimization of novel tools for cancer therapy. The employment of spherical inorganic microparticles, in particular, calcium carbonate vaterite microspheres, as microcarriers appears promising because of their porous, matrix structure, biocompatibility, and biodegradability. Here, we summarize the results of the development of the approaches to synthesis of calcium carbonate vaterite microspheres with narrowed size distribution and microencapsulation of low-molecular-weight anticancer drugs, such as doxorubicin hydrochloride into obtained microspheres. Supplementing the reaction mixture with a thickener defines fabrication of homogeneous vaterite microparticles with a spherical shape and an average size of 2 to 3 μm. Synthesised microspheres ensure prolonged release of doxorubicin at physiological pH values and can be used as a delivery system and as a structural component for development of a theranostic platform for tumour treatment and diagnosis.

2021, Karaulov, A., Sukhanova, A., Kalenichenko, D., Nifontova, G., Nabiev, I., Калениченко, Дарья Владимировна, Нифонтова, Галина Олеговна, Набиев, Игорь Руфаилович

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.The engineering of delivery systems for drugs and contrasting labels ensuring the simultaneous imaging and treatment of malignant tumors is an important hurdle in developing new tools for cancer therapy and diagnosis. Polyelectrolyte microcapsules (MCs), formed by nanosized interpolymer complexes, represent a promising platform for the designing of multipurpose agents, functionalized with various components, including high-and low-molecular-weight substances, metal nanoparticles, and organic fluorescent dyes. Here, we have developed size-homogenous MCs with different structures (core/shell and shell types) and microbeads containing doxorubicin (DOX) as a model anticancer drug, and fluorescent semiconductor nanocrystals (quantum dots, QDs) as fluorescent nanolabels. In this study, we suggest approaches to the encapsulation of DOX at different stages of the MC synthesis and describe the optimal conditions for the optical encoding of MCs with water-soluble QDs. The results of primary characterization of the designed microcarriers, including particle analysis, the efficacy of DOX and QDs encapsulation, and the drug release kinetics are reported. The polyelectrolyte MCs developed here ensure a modified (prolonged) release of DOX, under conditions close to normal and tumor tissues; they possess a bright fluorescence that paves the way to their exploitation for the delivery of antitumor drugs and fluorescence imaging.

2022, Nifontova, G., Nabiev, I., Sukhanova, A., Набиев, Игорь Руфаилович

Abstract Label-free bioanalytical methods have been widely employed in biomedical research, in particular, in drug screening and discovery, diagnostics, and proteomics. Photonic crystals (PCs) represent a modern alternative to surface plasmon resonance (SPR) techniques. Imaging of PC surface modes has been demonstrated as a promising label-free approach allowing for multiplexed detection. Surface modification of PC sensors is an important stage determining the effectiveness of the analysis of biomolecule interactions. Here, we describe the results of the development of a label-free PC-based sensor, the key steps of the modification and functionalization of the PC surface with proteins, as well as the evaluation of its suitability for sensing via 2D imaging of binding events. Our data demonstrate the efficiency of the designed PC-based sensor for analysis of proteins interactions and pave the way for the engineering of a label-free biosensing platform based on PCs.

2021, Sukhanova, A., Ramos-Gomes, F., Chames, P., Baty, D., Sokolov, P., Nabiev, I., Соколов, Павел Михайлович, Набиев, Игорь Руфаилович

© 2021, Springer Science+Business Media, LLC, part of Springer Nature.Early detection of malignant tumors, micrometastases, and disseminated tumor cells is one of the effective way of fighting cancer. Among the many existing imaging methods like computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), optical imaging with fluorescent probes is one of the most promising alternatives because it is fast, inexpensive, safe, sensitive, and specific. However, traditional fluorescent probes, based on organic fluorescent dyes, suffer from the low signal-to-noise ratio. Furthermore, conventional organic fluorescent dyes are unsuitable for deep tissue imaging because of the strong visible light absorption by biological tissues. The use of fluorescent semiconductor nanocrystals, or quantum dots (QDs), may overcome this limitation due to their large multiphoton cross section, which ensures efficient imaging of thick tissue sections inaccessible with conventional fluorescent probes. Moreover, the lower photobleaching and higher brightness of fluorescence signals from QDs ensures a much better discrimination of positive signals from the background. The use of fluorescent nanoprobes based on QDs conjugated to uniformly oriented high-affinity single-domain antibodies (sdAbs) may significantly increase the sensitivity and specificity due to better recognition of analytes and deeper penetration into tissues due to small size of such nanoprobes. Here, we describe a protocol for the fabrication of nanoprobes based on sdAbs and QDs, preparation of experimental xenograft mouse models for quality control, and multiphoton imaging of deep-tissue solid tumors, micrometastases, and disseminated tumor cells.

2022, Nifontova, G., Tsoi, T., Karaulov, A., Nabiev, I., Sukhanova, A., Цой, Татьяна Дмитриевна, Набиев, Игорь Руфаилович

The targeted delivery of cancer drugs to tumor-specific molecular targets represents a major challenge in modern personalized cancer medicine. Engineering of micron and submicron polymeric multilayer capsules allows the obtaining of multifunctional theranostic systems serving as controllable stimulus-responsive tools with a high clinical potential to be used in cancer therapy and detection. The functionalities of such theranostic systems are determined by the design and structural properties of the capsules. This review (1) describes the current issues in designing cancer cell-targeting polymeric multilayer capsules, (2) analyzes the effects of the interactions of the capsules with the cellular and molecular constituents of biological fluids, and (3) presents the key structural parameters determining the effectiveness of capsule targeting. The influence of the morphological and physicochemical parameters and the origin of the structural components and surface ligands on the functional activity of polymeric multilayer capsules at the molecular, cellular, and whole-body levels are summarized. The basic structural and functional principles determining the future trends of theranostic capsule development are established and discussed. © 2022 The Royal Society of Chemistry.

2019, Ramos-Gomes, F., Alves, F., Sukhanova, A., Nifontova, G., Baryshnikova, M., Nabiev, I., Нифонтова, Галина Олеговна, Барышникова, Мария Анатольевна, Набиев, Игорь Руфаилович

© 2019 SPIE.Quantum dots (QDs) are fluorescent semiconductor nanocrystals with a high photostability, wide absorption spectra, and narrow, size-tunable emission spectra, which make them promising nanolabels to be encapsulated in microcarriers used as bioimaging and theranostic tools. Here, we describe an approach to the optical encoding of polyelectrolyte microcapsules with the prepared stable water-soluble QDs and key stages of surface functionalization of these microcapsules with cetuximab, humanised monoclonal anticancer antibody. Obtained conjugates demonstrate the specificity and efficiency of the engineered system as a cancer cell-targeted tracing tool that could be used for cancer diagnosis, treatment and monitoring of cancer therapy.