Ekaterina Prikhozhdenko - Academia.edu (original) (raw)

Papers by Ekaterina Prikhozhdenko

Research paper thumbnail of Combination of Machine Learning and Raman Spectroscopy for Determination of the Complex of Whey Protein Isolate with Hyaluronic Acid

Research paper thumbnail of Carbon Nanotube Microscale Fiber Grid as an Advanced Calibration System for Multispectral Optoacoustic Imaging

Research paper thumbnail of Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study

ACS Applied Materials & Interfaces, May 19, 2023

Research paper thumbnail of Solvothermal synthesis of hydrophobic carbon dots in reversed micelles

Journal of Nanoparticle Research, Sep 1, 2018

Synthesis of hydrophobic luminescent carbon nanostructures in non-aqueous solution has been perfo... more Synthesis of hydrophobic luminescent carbon nanostructures in non-aqueous solution has been performed. The system consisted of hexane as nonpolar Boilp hase, nonionic polyoxyethylene (4) lauryl ether (Brij L4) as a surfactant, and either water or dextran sulfate aqueous solution as a polar phase. Carbon nanodots (CND) with a particle size of 5.0 ± 0.7 nm were formed by solvothermal treatment at 180°C of two-(hexane-Brij L4) and threecomponent (hexane-Brij L4-aqua solutions) systems. It was found that CND with blue-green-yellow photoluminescence (PL) with linear dependence of emission peak position on excitation wavelength and stability of PL over at least 3 weeks were formed from Brij L4. We found that using small volume of water as the third component helps to reorganize Brij L4 molecules which results in CND PL intensity increase by a factor of 1.5 and quantum yield increase from 2.0 to 2.6% compared to CND from the two-component micellar system. Replacing water with dextran sulfate solution resulted in a lower quantum yield to 2.2%. Thus, addition of small amount of water clearly shows an effect of molecular level organization on properties of CND and results in enhanced quantum yield.

Research paper thumbnail of Composite multilayer films based on polyelectrolytes and in situ ‐formed carbon nanostructures with enhanced photoluminescence and conductivity properties

Journal of Applied Polymer Science, Mar 21, 2019

We report a facile route for the fabrication of thin composite films based on polyelectrolytes an... more We report a facile route for the fabrication of thin composite films based on polyelectrolytes and carbon nanostructures. Composite films were made by layer-by-layer assembly of polyelectrolyte multilayers utilizing embedded dextran sulfate (Dex) solution as a carbon source. Raman measurements indicate the formation of carbon nanostructures from the Dex precursor over the whole film. Formation of these nanostructures results in enhanced photoluminescence and an increase in conductivity by two orders of magnitude to about 0.055 S cm −1. The latter corresponds to the level of wide-gap semiconductors, in contrast to the initial insulating polyelectrolyte film. A distinct peak of photoluminescence of the films is found in the blue region at the wavelength of 450 nm.

Research paper thumbnail of Magnetic Platelets as a Platform for Drug Delivery and Cell Trapping

Pharmaceutics, Jan 7, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Live Cell Poration by Au Nanostars to Probe Intracellular Molecular Composition with SERS

Nanomaterials, Sep 30, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Effect of Size on Magnetic Polyelectrolyte Microcapsules Behavior: Biodistribution, Circulation Time, Interactions with Blood Cells and Immune System

Pharmaceutics, Dec 14, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Thermal carbonization in nanoscale reactors: controlled formation of carbon nanodots inside porous CaCO3 microparticles

Scientific Reports, Jun 20, 2018

Synthesis of carbon nanodots (CNDs) in confined geometry via incorporation of dextran sulphate in... more Synthesis of carbon nanodots (CNDs) in confined geometry via incorporation of dextran sulphate into pores of CaCO 3 microparticles is demonstrated. The preparation process included three steps: coprecipitation of solutions of inorganic salts and carbon source, thermal treatment and CaCO 3 matrix removal. We show that geometric constraints can be used to precisely control the amount of source material and to avoid formation of large carbon particles. Analysis of TEM data shows particle size of ~3.7 nm with narrow size distribution. Furthermore, we found that variation in pore morphology has a clear effect on CNDs structure and optical properties. CNDs with graphene oxide like structure were obtained in the nanoporous outer shell layer of CaCO 3 microparticles, while less ordered CNDs with the evidence of complex disordered carbons were extracted from the inner microcavity. These results suggest that confined volume synthesis route in CaCO3 nanopores can be used to precisely control the structure and optical properties of CNDs. Light emitting carbon nanodots (CNDs) have recently emerged as a new family of low dimensional nanocarbon materials. Compared to the more conventional light emitting quantum dots (e.g. CdSe, CdS, Si and Ge etc.), CNDs have clear advantages 1-4 such as low environmental impact, low cytotoxicity, excitation-dependent emission wavelength, excellent biocompatibility, tunable surface functionalities, stability under ambient conditions. These appealing properties of CNDs suggest great opportunities for applications ranging from consumer electronics 5 , to light harvesting 6-8 and biological cell imaging 7. As a consequence, the field has been growing rapidly with thousands of articles published over the last few years. One of the major approaches to synthesis of CNDs is "bottom-up" preparation of structured materials via controlled assembly of atoms and molecules. This approach allows the synthesis of CNDs from a wide variety of molecular precursors-mainly carbon sources with diverse properties and composition. Vast majority of the synthesis routes involve high-temperature treatment options: pyrolysis 9 , ultrasonic 4,10-12 or microwave radiation 13-18 , solvotermal 19,20 and hydrothermal carbonization methods 21-24. The latter route being particularly widespread due to its relative simplicity. The main problems arising in the synthesis of CNDs are non-uniformity in morphology and size distribution, formation of by-products, in particular, large carbon particles 8,25-29. The heterogeneous nature of the reaction products is a consequence of relatively poor control over the synthesis environment since the molecular diffusion, temperature fluctuations and particle growth conditions cannot be effectively controlled on the nanoscale level in large volume reactors. Micro-and nano-porous structures are a promising type of synthesis environment because of a possibility to perform reaction in a restricted volume with precisely controlled amount of reagents. There are a number of advantages in using porous structures as reaction volumes such as varying the size and morphology of the pores and access to a variety of matrixes (including metals, silica, inorganic and organic particles 30-32 and polymers 33,34). Furthermore, pore geometry may have a significant effect on carbon-based systems in particular by influencing preference for configurations with sp, sp 2 and sp 3 hybridizations (bonding) and hence can be used to control the atomic structure and functionality of the final product.

Research paper thumbnail of Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency <i>in vitro</i> and <i>in vivo</i>

Cytometry Part A, Jul 17, 2023

Research paper thumbnail of Dynamic blood flow phantom for in vivo liquid biopsy standardization

Scientific Reports, Jan 13, 2021

In vivo liquid biopsy, especially using the photoacoustic (PA) method, demonstrated high clinical... more In vivo liquid biopsy, especially using the photoacoustic (PA) method, demonstrated high clinical potential for early diagnosis of deadly diseases such as cancer, infections, and cardiovascular disorders through the detection of rare circulating tumor cells (CTCs), bacteria, and clots in the blood background. However, little progress has been made in terms of standardization of these techniques, which is crucial to validate their high sensitivity, accuracy, and reproducibility. In the present study, we addressed this important demand by introducing a dynamic blood vessel phantom with flowing mimic normal and abnormal cells. The light transparent silica microspheres were used as white blood cells and platelets phantoms, while hollow polymeric capsules, filled with hemoglobin and melanin, reproduced red blood cells and melanoma CTCs, respectively. These phantoms were successfully used for calibration of the PA flow cytometry platform with high-speed signal processing. The results suggest that these dynamic cell flow phantoms with appropriate biochemical, optical, thermal, and acoustic properties can be promising for the establishment of standardization tool for calibration of PA, fluorescent, Raman, and other detection methods of in vivo flow cytometry and liquid biopsy. Early disease diagnosis is significantly limited by the absence of methods for high sensitivity detection of extremely low-level quantity of disease-related markers, such as circulating tumor cells (CTCs), pathogenic bacteria, viruses, clots, and sickle cells. Many methods have been explored for this purpose including fluorescence, Raman, and photoacoustic (PA) spectroscopy and microscopy techniques 1-3. PA imaging demonstrated significant benefits, such as deep penetration depth (up to 3-5 cm) to biological tissue 4 , safety, and noninvasiveness 1,5-10. However, PA imaging is relatively slow, which prevents the study of dynamic events. Among different PA techniques, PA flow cytometry (PAFC) demonstrated the ability to assess large volumes of patient's blood noninvasively in vivo, thus, allowing to detect ultralow concentrations of fast-moving pathological cells 11. PAFC diagnosis platform has recently demonstrated significant clinical potential for detection of rare CTCs 11 , infections (for example, malaria 12), exosomes 13 , bacteria, and blood clots (also called thrombi) 5,14,15. Specifically, clinical potential of PAFC was demonstrated through detection of unprecedentedly low CTC concentration in melanoma patients directly in the bloodstream at the level of 1 CTC in 1 L of blood, which is 1000-fold sensitivity threshold improvement 11. As a new diagnostic tool, the PAFC platform requires specialized standardization and calibration procedures using a phantom with appropriate optical (absorption, scattering), thermal (heat conductivity), acoustic (speed of sound, acoustic attenuation), and PA contrast properties to establish standardized PA metrics. Comparison of the PA platforms for microscopy, spectroscopy, cytometry, or tomography is challenging due to differences in schemes, modes, data processing and analysis. The signals during in vivo measurements vary from animal to animal or from patient to patient depending on the vessel's depth and size, flow rate, or skin pigmentation. For ex vivo measurements the blood properties after sample collection are changing quickly within a few hours, therefore, it is problematic to have stable blood parameters during a long time. Altogether, this makes it difficult to use blood for quantitative accurate calibration of PA techniques ex vivo. Thus, there is an urgent need to develop new PA-specific standardization and calibration strategy. One of the key components of the calibration procedure is to have biologically-adequate vessel phantoms with flowing mimic normal and abnormal cells. Different phantoms have been developed so far to calibrate PA techniques using various materials for biotissue properties' modeling, such as agar, bovine gelatin, polyvinyl alcohol, and silica 16,17 , as well as transparent

Research paper thumbnail of Degradation of Hybrid Drug Delivery Carriers with a Mineral Core and a Protein–Tannin Shell under Proteolytic Hydrolases

Biomimetics, May 12, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Lightsheet-based flow cytometer for whole blood with the ability for the magnetic retrieval of objects from the blood flow

Biomedical Optics Express, Dec 15, 2020

Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are... more Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are of great interest for modern diagnostics, but devices that can solve this problem for the whole blood volume of laboratory animals are still rare. Here we have developed SPIM-based lightsheet flow cytometer for the detection of fluorescently-labeled objects in whole blood. The bypass channel between two blood vessels connected with the external flow cell was used to visualize, detect, and magnetically separate fluorescently-labeled objects without hydrodynamic focusing. Carriers for targeted drug delivery were used as model objects to test the device performance. They were injected into the bloodstream of the rat, detected fluorescently, and then captured from the bloodstream by a magnetic separator prior to filtration in organs. Carriers extracted from the whole blood were studied by a number of in vitro methods.

Research paper thumbnail of Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety

Journal of Controlled Release, 2021

Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many... more Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many of them are lacking effectiveness for kidney targeting, due to systemic dispersion and accumulation in the lungs and liver after intravenous administration. Renal artery administration of carriers provides their effective local accumulation but may cause irreversible vessel blockage. Therefore, the combination of the correct administration procedure, suitable drug delivery system, selection of effective and safe dosage is the key to sparing local therapy. Here, we propose the 3-μm sized fluorescent capsules based on poly-L-arginine and dextran sulfate for targeting the kidney via a mice renal artery. Hemodynamic study of the target kidney in combination with the histological analysis reveals a safe dose of microcapsules (20 × 106), which has not lead to irreversible pathological changes in blood flow and kidney tissue, and provides retention of 20.5 ± 3% of the introduced capsules in the renal cortex glomeruli. Efficacy of fluorescent dye localization in the target kidney after intra-arterial administration is 9 times higher than in the opposite kidney and after intravenous injection. After 24 h microcapsules are not observed in the target kidney when the safe dose of carriers is being used but a high level of fluorescent signal persists for 48 h indicating that fluorescent cargo accumulation in tissues. Injection of non-safe microcapsule dose leads to carriers staying in glomeruli for at least 48 h which has consequences of blood flow not being restored and tissue damage being observed in histology.

Research paper thumbnail of Optoacoustic monitoring of bilirubin photodegradation

Journal of Biophotonics, Jul 8, 2023

Hematomas resulted from trauma are very common, and the efficacy of existing treatment techniques... more Hematomas resulted from trauma are very common, and the efficacy of existing treatment techniques is limited. Phototherapy can be used to expedite healing and improve the appearance of the damaged tissue. Efficient phototherapy requires determination of chromophore composition in hematoma, which can be provided by the optoacoustic (OA) technique, as it combines high spatial resolution and optical contrast. Here, we conducted experiments on photodegradation of bilirubin in gelatin slin phantoms. We have demonstrated that the OA technique allows monitoring of bilirubin concentration during photodegradation, and also distinguishing bilirubin concentration in depth. The obtained results suggest that OA monitoring may be used for efficient hematoma phototherapy.

Research paper thumbnail of Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency in vitro and in vivo

Research paper thumbnail of Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept

International Journal of Molecular Sciences

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonep... more Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy comb...

Research paper thumbnail of 3D printed system for rare objects magnetic separation from the bloodstream

Computational Biophysics and Nanobiophotonics

Research paper thumbnail of Effect of Surface Modification of Multifunctional Nanocomposite Drug Delivery Carriers with DARPin on Their Biodistribution In Vitro and In Vivo

ACS Applied Bio Materials

Research paper thumbnail of CaCO3-based carriers with prolonged release properties for antifungal drug delivery to hair follicles

Biomaterials Science

CaCO3 carriers are efficiently loaded with Griseofulvin antifungal drug (25% w/w). Stabilizing co... more CaCO3 carriers are efficiently loaded with Griseofulvin antifungal drug (25% w/w). Stabilizing coating formation prolongs the carrier degradation and payload release. The proposed system enables delivery to hair follicles and bioavailability enhancement for Gf.

Research paper thumbnail of Combination of Machine Learning and Raman Spectroscopy for Determination of the Complex of Whey Protein Isolate with Hyaluronic Acid

Research paper thumbnail of Carbon Nanotube Microscale Fiber Grid as an Advanced Calibration System for Multispectral Optoacoustic Imaging

Research paper thumbnail of Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study

ACS Applied Materials & Interfaces, May 19, 2023

Research paper thumbnail of Solvothermal synthesis of hydrophobic carbon dots in reversed micelles

Journal of Nanoparticle Research, Sep 1, 2018

Synthesis of hydrophobic luminescent carbon nanostructures in non-aqueous solution has been perfo... more Synthesis of hydrophobic luminescent carbon nanostructures in non-aqueous solution has been performed. The system consisted of hexane as nonpolar Boilp hase, nonionic polyoxyethylene (4) lauryl ether (Brij L4) as a surfactant, and either water or dextran sulfate aqueous solution as a polar phase. Carbon nanodots (CND) with a particle size of 5.0 ± 0.7 nm were formed by solvothermal treatment at 180°C of two-(hexane-Brij L4) and threecomponent (hexane-Brij L4-aqua solutions) systems. It was found that CND with blue-green-yellow photoluminescence (PL) with linear dependence of emission peak position on excitation wavelength and stability of PL over at least 3 weeks were formed from Brij L4. We found that using small volume of water as the third component helps to reorganize Brij L4 molecules which results in CND PL intensity increase by a factor of 1.5 and quantum yield increase from 2.0 to 2.6% compared to CND from the two-component micellar system. Replacing water with dextran sulfate solution resulted in a lower quantum yield to 2.2%. Thus, addition of small amount of water clearly shows an effect of molecular level organization on properties of CND and results in enhanced quantum yield.

Research paper thumbnail of Composite multilayer films based on polyelectrolytes and in situ ‐formed carbon nanostructures with enhanced photoluminescence and conductivity properties

Journal of Applied Polymer Science, Mar 21, 2019

We report a facile route for the fabrication of thin composite films based on polyelectrolytes an... more We report a facile route for the fabrication of thin composite films based on polyelectrolytes and carbon nanostructures. Composite films were made by layer-by-layer assembly of polyelectrolyte multilayers utilizing embedded dextran sulfate (Dex) solution as a carbon source. Raman measurements indicate the formation of carbon nanostructures from the Dex precursor over the whole film. Formation of these nanostructures results in enhanced photoluminescence and an increase in conductivity by two orders of magnitude to about 0.055 S cm −1. The latter corresponds to the level of wide-gap semiconductors, in contrast to the initial insulating polyelectrolyte film. A distinct peak of photoluminescence of the films is found in the blue region at the wavelength of 450 nm.

Research paper thumbnail of Magnetic Platelets as a Platform for Drug Delivery and Cell Trapping

Pharmaceutics, Jan 7, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Live Cell Poration by Au Nanostars to Probe Intracellular Molecular Composition with SERS

Nanomaterials, Sep 30, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Effect of Size on Magnetic Polyelectrolyte Microcapsules Behavior: Biodistribution, Circulation Time, Interactions with Blood Cells and Immune System

Pharmaceutics, Dec 14, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Thermal carbonization in nanoscale reactors: controlled formation of carbon nanodots inside porous CaCO3 microparticles

Scientific Reports, Jun 20, 2018

Synthesis of carbon nanodots (CNDs) in confined geometry via incorporation of dextran sulphate in... more Synthesis of carbon nanodots (CNDs) in confined geometry via incorporation of dextran sulphate into pores of CaCO 3 microparticles is demonstrated. The preparation process included three steps: coprecipitation of solutions of inorganic salts and carbon source, thermal treatment and CaCO 3 matrix removal. We show that geometric constraints can be used to precisely control the amount of source material and to avoid formation of large carbon particles. Analysis of TEM data shows particle size of ~3.7 nm with narrow size distribution. Furthermore, we found that variation in pore morphology has a clear effect on CNDs structure and optical properties. CNDs with graphene oxide like structure were obtained in the nanoporous outer shell layer of CaCO 3 microparticles, while less ordered CNDs with the evidence of complex disordered carbons were extracted from the inner microcavity. These results suggest that confined volume synthesis route in CaCO3 nanopores can be used to precisely control the structure and optical properties of CNDs. Light emitting carbon nanodots (CNDs) have recently emerged as a new family of low dimensional nanocarbon materials. Compared to the more conventional light emitting quantum dots (e.g. CdSe, CdS, Si and Ge etc.), CNDs have clear advantages 1-4 such as low environmental impact, low cytotoxicity, excitation-dependent emission wavelength, excellent biocompatibility, tunable surface functionalities, stability under ambient conditions. These appealing properties of CNDs suggest great opportunities for applications ranging from consumer electronics 5 , to light harvesting 6-8 and biological cell imaging 7. As a consequence, the field has been growing rapidly with thousands of articles published over the last few years. One of the major approaches to synthesis of CNDs is "bottom-up" preparation of structured materials via controlled assembly of atoms and molecules. This approach allows the synthesis of CNDs from a wide variety of molecular precursors-mainly carbon sources with diverse properties and composition. Vast majority of the synthesis routes involve high-temperature treatment options: pyrolysis 9 , ultrasonic 4,10-12 or microwave radiation 13-18 , solvotermal 19,20 and hydrothermal carbonization methods 21-24. The latter route being particularly widespread due to its relative simplicity. The main problems arising in the synthesis of CNDs are non-uniformity in morphology and size distribution, formation of by-products, in particular, large carbon particles 8,25-29. The heterogeneous nature of the reaction products is a consequence of relatively poor control over the synthesis environment since the molecular diffusion, temperature fluctuations and particle growth conditions cannot be effectively controlled on the nanoscale level in large volume reactors. Micro-and nano-porous structures are a promising type of synthesis environment because of a possibility to perform reaction in a restricted volume with precisely controlled amount of reagents. There are a number of advantages in using porous structures as reaction volumes such as varying the size and morphology of the pores and access to a variety of matrixes (including metals, silica, inorganic and organic particles 30-32 and polymers 33,34). Furthermore, pore geometry may have a significant effect on carbon-based systems in particular by influencing preference for configurations with sp, sp 2 and sp 3 hybridizations (bonding) and hence can be used to control the atomic structure and functionality of the final product.

Research paper thumbnail of Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency <i>in vitro</i> and <i>in vivo</i>

Cytometry Part A, Jul 17, 2023

Research paper thumbnail of Dynamic blood flow phantom for in vivo liquid biopsy standardization

Scientific Reports, Jan 13, 2021

In vivo liquid biopsy, especially using the photoacoustic (PA) method, demonstrated high clinical... more In vivo liquid biopsy, especially using the photoacoustic (PA) method, demonstrated high clinical potential for early diagnosis of deadly diseases such as cancer, infections, and cardiovascular disorders through the detection of rare circulating tumor cells (CTCs), bacteria, and clots in the blood background. However, little progress has been made in terms of standardization of these techniques, which is crucial to validate their high sensitivity, accuracy, and reproducibility. In the present study, we addressed this important demand by introducing a dynamic blood vessel phantom with flowing mimic normal and abnormal cells. The light transparent silica microspheres were used as white blood cells and platelets phantoms, while hollow polymeric capsules, filled with hemoglobin and melanin, reproduced red blood cells and melanoma CTCs, respectively. These phantoms were successfully used for calibration of the PA flow cytometry platform with high-speed signal processing. The results suggest that these dynamic cell flow phantoms with appropriate biochemical, optical, thermal, and acoustic properties can be promising for the establishment of standardization tool for calibration of PA, fluorescent, Raman, and other detection methods of in vivo flow cytometry and liquid biopsy. Early disease diagnosis is significantly limited by the absence of methods for high sensitivity detection of extremely low-level quantity of disease-related markers, such as circulating tumor cells (CTCs), pathogenic bacteria, viruses, clots, and sickle cells. Many methods have been explored for this purpose including fluorescence, Raman, and photoacoustic (PA) spectroscopy and microscopy techniques 1-3. PA imaging demonstrated significant benefits, such as deep penetration depth (up to 3-5 cm) to biological tissue 4 , safety, and noninvasiveness 1,5-10. However, PA imaging is relatively slow, which prevents the study of dynamic events. Among different PA techniques, PA flow cytometry (PAFC) demonstrated the ability to assess large volumes of patient's blood noninvasively in vivo, thus, allowing to detect ultralow concentrations of fast-moving pathological cells 11. PAFC diagnosis platform has recently demonstrated significant clinical potential for detection of rare CTCs 11 , infections (for example, malaria 12), exosomes 13 , bacteria, and blood clots (also called thrombi) 5,14,15. Specifically, clinical potential of PAFC was demonstrated through detection of unprecedentedly low CTC concentration in melanoma patients directly in the bloodstream at the level of 1 CTC in 1 L of blood, which is 1000-fold sensitivity threshold improvement 11. As a new diagnostic tool, the PAFC platform requires specialized standardization and calibration procedures using a phantom with appropriate optical (absorption, scattering), thermal (heat conductivity), acoustic (speed of sound, acoustic attenuation), and PA contrast properties to establish standardized PA metrics. Comparison of the PA platforms for microscopy, spectroscopy, cytometry, or tomography is challenging due to differences in schemes, modes, data processing and analysis. The signals during in vivo measurements vary from animal to animal or from patient to patient depending on the vessel's depth and size, flow rate, or skin pigmentation. For ex vivo measurements the blood properties after sample collection are changing quickly within a few hours, therefore, it is problematic to have stable blood parameters during a long time. Altogether, this makes it difficult to use blood for quantitative accurate calibration of PA techniques ex vivo. Thus, there is an urgent need to develop new PA-specific standardization and calibration strategy. One of the key components of the calibration procedure is to have biologically-adequate vessel phantoms with flowing mimic normal and abnormal cells. Different phantoms have been developed so far to calibrate PA techniques using various materials for biotissue properties' modeling, such as agar, bovine gelatin, polyvinyl alcohol, and silica 16,17 , as well as transparent

Research paper thumbnail of Degradation of Hybrid Drug Delivery Carriers with a Mineral Core and a Protein–Tannin Shell under Proteolytic Hydrolases

Biomimetics, May 12, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Lightsheet-based flow cytometer for whole blood with the ability for the magnetic retrieval of objects from the blood flow

Biomedical Optics Express, Dec 15, 2020

Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are... more Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are of great interest for modern diagnostics, but devices that can solve this problem for the whole blood volume of laboratory animals are still rare. Here we have developed SPIM-based lightsheet flow cytometer for the detection of fluorescently-labeled objects in whole blood. The bypass channel between two blood vessels connected with the external flow cell was used to visualize, detect, and magnetically separate fluorescently-labeled objects without hydrodynamic focusing. Carriers for targeted drug delivery were used as model objects to test the device performance. They were injected into the bloodstream of the rat, detected fluorescently, and then captured from the bloodstream by a magnetic separator prior to filtration in organs. Carriers extracted from the whole blood were studied by a number of in vitro methods.

Research paper thumbnail of Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety

Journal of Controlled Release, 2021

Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many... more Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many of them are lacking effectiveness for kidney targeting, due to systemic dispersion and accumulation in the lungs and liver after intravenous administration. Renal artery administration of carriers provides their effective local accumulation but may cause irreversible vessel blockage. Therefore, the combination of the correct administration procedure, suitable drug delivery system, selection of effective and safe dosage is the key to sparing local therapy. Here, we propose the 3-μm sized fluorescent capsules based on poly-L-arginine and dextran sulfate for targeting the kidney via a mice renal artery. Hemodynamic study of the target kidney in combination with the histological analysis reveals a safe dose of microcapsules (20 × 106), which has not lead to irreversible pathological changes in blood flow and kidney tissue, and provides retention of 20.5 ± 3% of the introduced capsules in the renal cortex glomeruli. Efficacy of fluorescent dye localization in the target kidney after intra-arterial administration is 9 times higher than in the opposite kidney and after intravenous injection. After 24 h microcapsules are not observed in the target kidney when the safe dose of carriers is being used but a high level of fluorescent signal persists for 48 h indicating that fluorescent cargo accumulation in tissues. Injection of non-safe microcapsule dose leads to carriers staying in glomeruli for at least 48 h which has consequences of blood flow not being restored and tissue damage being observed in histology.

Research paper thumbnail of Optoacoustic monitoring of bilirubin photodegradation

Journal of Biophotonics, Jul 8, 2023

Hematomas resulted from trauma are very common, and the efficacy of existing treatment techniques... more Hematomas resulted from trauma are very common, and the efficacy of existing treatment techniques is limited. Phototherapy can be used to expedite healing and improve the appearance of the damaged tissue. Efficient phototherapy requires determination of chromophore composition in hematoma, which can be provided by the optoacoustic (OA) technique, as it combines high spatial resolution and optical contrast. Here, we conducted experiments on photodegradation of bilirubin in gelatin slin phantoms. We have demonstrated that the OA technique allows monitoring of bilirubin concentration during photodegradation, and also distinguishing bilirubin concentration in depth. The obtained results suggest that OA monitoring may be used for efficient hematoma phototherapy.

Research paper thumbnail of Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency in vitro and in vivo

Research paper thumbnail of Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept

International Journal of Molecular Sciences

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonep... more Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy comb...

Research paper thumbnail of 3D printed system for rare objects magnetic separation from the bloodstream

Computational Biophysics and Nanobiophotonics

Research paper thumbnail of Effect of Surface Modification of Multifunctional Nanocomposite Drug Delivery Carriers with DARPin on Their Biodistribution In Vitro and In Vivo

ACS Applied Bio Materials

Research paper thumbnail of CaCO3-based carriers with prolonged release properties for antifungal drug delivery to hair follicles

Biomaterials Science

CaCO3 carriers are efficiently loaded with Griseofulvin antifungal drug (25% w/w). Stabilizing co... more CaCO3 carriers are efficiently loaded with Griseofulvin antifungal drug (25% w/w). Stabilizing coating formation prolongs the carrier degradation and payload release. The proposed system enables delivery to hair follicles and bioavailability enhancement for Gf.