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result(s) for
"Popov, Anton"
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Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization
by
Zelepukin, Ivan V.
,
Shemyakov, Alexander E.
,
Deyev, Sergey M.
in
Ablation
,
Apoptosis - drug effects
,
Apoptosis - radiation effects
2024
Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes.
Journal Article
In vivo evaluation of safety, biodistribution and pharmacokinetics of laser-synthesized gold nanoparticles
by
Popov, Anton
,
Kabashin, Andrei V.
,
Esteve, Marie-Anne
in
639/925/352/2733
,
639/925/928/1070
,
64/60
2019
Capable of generating plasmonic and other effects, gold nanostructures can offer a variety of diagnostic and therapy functionalities for biomedical applications, but conventional chemically-synthesized Au nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au nanoparticles (AuNP) present a viable alternative to chemical counterparts and can offer exceptional purity (no trace of contaminants) and unusual surface chemistry making possible direct conjugation with biocompatible polymers (dextran, polyethylene glycol). This work presents the first pharmacokinetics, biodistribution and safety study of laser-ablated dextran-coated AuNP (AuNPd) under intravenous administration in small animal model. Our data show that AuNPd are rapidly eliminated from the blood circulation and accumulated preferentially in liver and spleen, without inducing liver or kidney toxicity, as confirmed by the plasmatic ALAT and ASAT activities, and creatininemia values. Despite certain residual accumulation in tissues, we did not detect any sign of histological damage or inflammation in tissues, while IL-6 level confirmed the absence of any chronic inflammation. The safety of AuNPd was confirmed by healthy behavior of animals and the absence of acute and chronic toxicities in liver, spleen and kidneys. Our results demonstrate that laser-synthesized AuNP are safe for biological systems, which promises their successful biomedical applications.
Journal Article
Laser- synthesized TiN nanoparticles as promising plasmonic alternative for biomedical applications
by
Da Silva, Anabela
,
Kabashin, Andrei V.
,
Jones, Nicola
in
140/125
,
639/925/352/2733
,
639/925/357/354
2019
Exhibiting a red-shifted absorption/scattering feature compared to conventional plasmonic metals, titanium nitride nanoparticles (TiN NPs) look as very promising candidates for biomedical applications, but these applications are still underexplored despite the presence of extensive data for conventional plasmonic counterparts. Here, we report the fabrication of ultrapure, size-tunable TiN NPs by methods of femtosecond laser ablation in liquids and their biological testing. We show that TiN NPs demonstrate strong and broad plasmonic peak around 640–700 nm with a significant tail over 800 nm even for small NPs sizes (<7 nm).
In vitro
tests of laser-synthesized TiN NPs on cellular models evidence their low cytotoxicity and excellent cell uptake. We finally demonstrate a strong photothermal therapy effect on U87–MG cancer cell cultures using TiN NPs as sensitizers of local hyperthermia under near-infrared laser excitation. Based on absorption band in the region of relative tissue transparency and acceptable biocompatibility, laser-synthesized TiN NPs promise the advancement of biomedical modalities employing plasmonic effects, including absorption/scattering contrast imaging, photothermal therapy, photoacoustic imaging and SERS.
Journal Article
Boron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment
by
Zelepukin, Ivan V.
,
Shemyakov, Alexander E.
,
Deyev, Sergey M.
in
Ablation
,
Analysis
,
Approximation
2023
Proton therapy is one of the promising radiotherapy modalities for the treatment of deep-seated and unresectable tumors, and its efficiency can further be enhanced by using boron-containing substances. Here, we explore the use of elemental boron (B) nanoparticles (NPs) as sensitizers for proton therapy enhancement. Prepared by methods of pulsed laser ablation in water, the used B NPs had a mean size of 50 nm, while a subsequent functionalization of the NPs by polyethylene glycol improved their colloidal stability in buffers. Laser-synthesized B NPs were efficiently absorbed by MNNG/Hos human osteosarcoma cells and did not demonstrate any remarkable toxicity effects up to concentrations of 100 ppm, as followed from the results of the MTT and clonogenic assay tests. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell death under irradiation by a 160.5 MeV proton beam. The irradiation of MNNG/Hos cells at a dose of 3 Gy in the presence of 80 and 100 ppm of B NPs led to a 2- and 2.7-fold decrease in the number of formed cell colonies compared to control samples irradiated in the absence of NPs. The obtained data unambiguously evidenced the effect of a strong proton therapy enhancement mediated by B NPs. We also found that the proton beam irradiation of B NPs leads to the generation of reactive oxygen species (ROS), which evidences a possible involvement of the non-nuclear mechanism of cancer cell death related to oxidative stress. Offering a series of advantages, including a passive targeting option and the possibility of additional theranostic functionalities based on the intrinsic properties of B NPs (e.g., photothermal therapy or neutron boron capture therapy), the proposed concept promises a major advancement in proton beam-based cancer treatment.
Journal Article
Transition metal dichalcogenide nanospheres for high-refractive-index nanophotonics and biomedical theranostics
by
Ermolaev, Georgy A.
,
Novoselov, Kostya S.
,
Panova, Daria A.
in
Ablation
,
Applied Physical Sciences
,
Chalcogenides
2022
Recent developments in the area of resonant dielectric nanostructures have created attractive opportunities for concentrating and manipulating light at the nanoscale and the establishment of the new exciting field of all-dielectric nanophotonics. Transition metal dichalcogenides (TMDCs) with nanopatterned surfaces are especially promising for these tasks. Still, the fabrication of these structures requires sophisticated lithographic processes, drastically complicating application prospects. To bridge this gap and broaden the application scope of TMDC nanomaterials, we report here femtosecond laser-ablative fabrication of water-dispersed spherical TMDC (MoS₂ and WS₂) nanoparticles (NPs) of variable size (5 to 250 nm). Such NPs demonstrate exciting optical and electronic properties inherited from TMDC crystals, due to preserved crystalline structure, which offers a unique combination of pronounced excitonic response and high refractive index value, making possible a strong concentration of electromagnetic field in the NPs. Furthermore, such NPs offer additional tunability due to hybridization between the Mie and excitonic resonances. Such properties bring to life a number of nontrivial effects, including enhanced photoabsorption and photothermal conversion. As an illustration, we demonstrate that the NPs exhibit a very strong photothermal response, much exceeding that of conventional dielectric nanoresonators based on Si. Being in a mobile colloidal state and exhibiting superior optical properties compared to other dielectric resonant structures, the synthesized TMDC NPs offer opportunities for the development of next-generation nanophotonic and nanotheranostic platforms, including photothermal therapy and multimodal bioimaging.
Journal Article
Electroencephalograms during Mental Arithmetic Task Performance
by
Popov, Anton
,
Chernykh, Mariia
,
Tukaev, Sergii
in
Biology
,
Brain research
,
Cognition & reasoning
2019
This work has been carried out to support the investigation of the electroencephalogram (EEG) Fourier power spectral, coherence, and detrended fluctuation characteristics during performance of mental tasks. To this aim, the presented dataset contains International 10/20 system EEG recordings from subjects under mental cognitive workload (performing mental serial subtraction) and the corresponding reference background EEGs. Based on the subtraction task performance (number of subtractions and accuracy of the result), the subjects were divided into good counters and bad counters (for whom the mental task required excessive efforts). The data was recorded from 36 healthy volunteers of matched age, all of whom are students of Educational and Scientific Centre “Institute of Biology and Medicine”, National Taras Shevchenko University of Kyiv (Ukraine); the recordings are available through Physiobank platform. The dataset can be used by the neuroscience research community studying brain dynamics during cognitive workload.
Journal Article
Recent Advances in Glucose Biosensors
by
Popov, Anton
,
German, Natalija
in
Artificial intelligence
,
Biosensing Techniques - methods
,
Biosensors
2026
The global burden of diabetes continues to grow, and the disease ranks among the leading causes of death and disability worldwide; it is projected that by 2050, the number of people living with this disease will exceed 1 [...]
Journal Article
Modeling suggests that oblique extension facilitates rifting and continental break-up
by
Popov, Anton A.
,
Sobolev, Stephan V.
,
Brune, Sascha
in
continental break-up
,
Earth sciences
,
Earth, ocean, space
2012
In many cases the initial stage of continental break‐up was and is associated with oblique rifting. That includes break‐up in the Southern and Equatorial Atlantic, separation from eastern and western Gondwana as well as many recent rift systems, like Gulf of California, Ethiopia Rift and Dead Sea fault. Using a simple analytic mechanical model and advanced numerical, thermomechanical modeling techniques we investigate the influence of oblique extension on the required tectonic force in a three‐dimensional setting. While magmatic processes have been already suggested to affect rift evolution, we show that additional mechanisms emerge due to the three‐dimensionality of an extensional system. Focusing on non‐magmatic rift settings, we find that oblique extension significantly facilitates the rift process. This is due to the fact that oblique deformation requires less force in order to reach the plastic yield limit than rift‐perpendicular extension. The model shows that in the case of two competing non‐magmatic rifts, with one perpendicular and one oblique to the direction of extension but otherwise having identical properties, the oblique rift zone is mechanically preferred and thus attracts more strain. Key Points Oblique extension facilitates the rift process in non‐magmatic settings Shearing a continent requires up to two times less force than rifting it An oblique rift zone attracts more strain than a competitive normal rift
Journal Article
Reduced Graphene Oxide and Polyaniline Nanofibers Nanocomposite for the Development of an Amperometric Glucose Biosensor
by
Popov, Anton
,
Aukstakojyte, Ruta
,
Barkauskas, Jurgis
in
Aniline Compounds
,
Aqueous solutions
,
Biosensing Techniques
2021
The control of glucose concentration is a crucial factor in clinical diagnosis and the food industry. Electrochemical biosensors based on reduced graphene oxide (rGO) and conducting polymers have a high potential for practical application. A novel thermal reduction protocol of graphene oxide (GO) in the presence of malonic acid was applied for the synthesis of rGO. The rGO was characterized by scanning electron microscopy, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, and Raman spectroscopy. rGO in combination with polyaniline (PANI), Nafion, and glucose oxidase (GOx) was used to develop an amperometric glucose biosensor. A graphite rod (GR) electrode premodified with a dispersion of PANI nanostructures and rGO, Nafion, and GOx was proposed as the working electrode of the biosensor. The optimal ratio of PANI and rGO in the dispersion used as a matrix for GOx immobilization was equal to 1:10. The developed glucose biosensor was characterized by a wide linear range (from 0.5 to 50 mM), low limit of detection (0.089 mM), good selectivity, reproducibility, and stability. Therefore, the developed biosensor is suitable for glucose determination in human serum. The PANI nanostructure and rGO dispersion is a promising material for the construction of electrochemical glucose biosensors.
Journal Article
Polyacrylic Acid-Coated LaB6 Nanoparticles as Efficient Sensitizers for Binary Proton Therapy
by
Kotelnikova, Polina A.
,
Shemyakov, Alexander E.
,
Soldatova, Olga V.
in
antitumor efficacy
,
Apoptosis
,
Boron
2025
Proton beam therapy (PBT) is a rapidly advancing modality of hadron therapy. The primary advantage of proton therapy lies in a unique depth-dose distribution characterized by the Bragg peak, which enables a highly targeted irradiation of the area limited to the tumor, while minimizing the impact on healthy tissues. However, a broader clinical adoption of the ion beam therapy is limited by both economic and radiobiological constraints. One of the possible ways to increase the relative biological effectiveness (RBE) of proton therapy involves the use of radiosensitizers. Background/Objectives: In this work, we investigated the efficacy of using colloidal solutions of lanthanum hexaboride (LaB6) nanoparticles (NPs) coated with polyacrylic acid (PAA) as sensitizers to increase the antitumor biological effectiveness of proton irradiation. This material has not yet been studied extensively so far, despite its promising physical and chemical properties and several reports on its biocompatibility. Methods: LaB6 NPs were synthesized by femtosecond pulsed laser ablation, functionalized with PAA and characterized. The safety of NPs was evaluated in vitro using a Live/Dead assay on cell cultures: EMT6/P, BT-474, and in vivo in Balb/c mice after intravenous (i.v.) administration. The efficacy of binary proton therapy was evaluated in vitro on cell cultures: EMT6/P, BT-474, and in vivo in the model of human ductal carcinoma of the mammary gland BT-474 in female Nu/j mice after intratumoral (i.t.) administration at a dose of 2.0 mg/mouse and local proton irradiation (fractional exposure of 31 Gy + 15 Gy). The biodistribution of LaB6-PAA NPs in the animal body was also evaluated. Results: Significant enhancement in cancer cell death following proton beam irradiation was demonstrated in vitro on EMT6/P, BT-474 cell lines. Although the antitumor efficacy observed in vivo was comparatively lower—likely due to the high sensitivity of the BT-474 xenografts—both proton monotherapy and binary treatment were well tolerated. Conclusions: LaB6-PAA NPs show promise as efficient sensitizers capable of enhancing the biological efficacy of proton therapy, offering a potential path forward for improving therapeutic outcomes.
Journal Article