2019, Tischenko, V. K., Mikhailovskaya, A. A., Popov, A. A., Tselikov, G., Petriev, V. M., Deyev, S. M., Timoshenko, V. Y., Prasad, P. N., Zavestovskaya, I. N., Kabashin, A. V., Деев, Сергей Михайлович, Тимошенко, Виктор Юрьевич, Завестовская, Ирина Николаевна, Кабашин, Андрей Викторович

© 2019, The Author(s). Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188 Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188 Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188 Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188 Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.

2019, Rogov, A., Ryabchikov, Y. V., Geloen, A., Tishchenko, I., Kharin, A. Y., Lysenko, V., Zavestovskaya, I. N., Kabashin, A. V., Timoshenko, V. Y., Завестовская, Ирина Николаевна, Кабашин, Андрей Викторович, Тимошенко, Виктор Юрьевич

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Presenting a safe alternative to conventional compound quantum dots and other functional nanostructures, nanosilicon can offer a series of breakthrough hyperthermia-based therapies under near-infrared, radiofrequency, ultrasound, etc., excitation, but the size range to sensitize these therapies is typically too large (>10 nm) to enable efficient imaging functionality based on photoluminescence properties of quantum-confined excitonic states. Here, it is shown that large Si nanoparticles (NPs) are capable of providing two-photon excited luminescence (TPEL) and second harmonic generation (SHG) responses, much exceeding that of smaller Si NPs, which promises their use as probes for bi-modal nonlinear optical bioimaging. It is finally demonstrated that the combination of TPEL and SHG channels makes possible efficient tracing of both separated Si NPs and their aggregations in different cell compartments, while the resolution of such an approach is enough to obtain 3D images. The obtained bi-modal contrast provides lacking imaging functionality for large Si NPs and promises the development of novel cancer theranostic modalities on their basis.

2019, Nirwan, V. P., Al-Kattan, A., Fahmi, A., Kabashin, A. V., Кабашин, Андрей Викторович

© 2019 by the authors. Licensee MDPI, Basel, Switzerland.We report a methodology for the fabrication of neutralized chitosan-based nanofiber matrices decorated with bare Au nanoparticles, which demonstrate stable characteristics even after prolonged contact with a biological environment. The methodology consists of electrospinning of a mixture of bare (ligand-free) laser-synthesized Au nanoparticles (AuNPs) and solutions of chitosan/polyethylene oxide (ratio 1/3) containing chitosan of a relatively high molecular weight (200 kDa) and concentration of 3% (w/v). Our studies reveal a continuous morphology of hybrid nanofibers with the mean fiber diameter of 189 nm ± 86 nm, which demonstrate a high thermal stability. Finally, we describe a protocol for the neutralization of nanofibers, which enabled us to achieve their structural stability in phosphate-buffered saline (PBS) for more than six months, as confirmed by microscopy and FTIR measurements. The formed hybrid nanofibers exhibit unique physicochemical properties essential for the development of future tissue engineering platforms.

2020, Muratov, A. V., Fronya, A. A., Antonenko, S. V., Kharin, A. Y., Aleshchenko, Y. A., Derzhavin, S. I., Karpov, N. V., Dombrovska, Y. I., Garmash, A. A., Kargin, N. I., Klimentov, S. M., Timoshenko, V. Y., Kabashin, A. V., Фроня, Анастасия Андреевна, Антоненко, Сергей Васильевич, Алещенко, Юрий Анатольевич, Гармаш, Александр Александрович, Каргин, Николай Иванович, Климентов, Сергей Михайлович, Тимошенко, Виктор Юрьевич, Кабашин, Андрей Викторович

Using methods of pulsed laser ablation from a silicon target in helium (He)-nitrogen (N2) gas mixtures maintained at reduced pressures (0.5-5 Torr), we fabricated substrate-supported silicon (Si) nanocrystal-based films exhibiting a strong photoluminescence (PL) emission, which depended on the He/N2 ratio. We show that, in the case of ablation in pure He gas, Si nanocrystals exhibit PL bands centered in the "red - near infrared" (maximum at 760 nm) and "green" (centered at 550 nm) spectral regions, which can be attributed to quantum-confined excitonic states in small Si nanocrystals and to local electronic states in amorphous silicon suboxide (a-SiOx) coating, respectively, while the addition of N2 leads to the generation of an intense "green-yellow" PL band centered at 580 nm. The origin of the latter band is attributed to a radiative recombination in amorphous oxynitride (a-SiNxOy) coating of Si nanocrystals. PL transients of Si nanocrystals with SiOx and a-SiNxOy coatings demonstrate nonexponential decays in the micro- and submicrosecond time scales with rates depending on nitrogen content in the mixture. After milling by ultrasound and dispersing in water, Si nanocrystals can be used as efficient non-toxic markers for bioimaging, while the observed spectral tailoring effect makes possible an adjustment of the PL emission of such markers to a concrete bioimaging task.

2019, Bailly, A. -L., Correard, F., Tselikov, G., Chaspoul, F., Popov, A., Kabashin, A. V., Попов, Антон Александрович, Кабашин, Андрей Викторович

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.

2019, Tselikov, G., Al-Kattan, A., Popov, A. A., Kabashin, A. V., Попов, Антон Александрович, Кабашин, Андрей Викторович

Copyright © 2019 SPIE.Methods of femtosecond laser ablation and fragmentation in liquids were used to fabricate bare (ligand-free) plasmonic Au and TiN nanoparticles. By varying laser parameters (laser energy, focusing conditions) and environment (deionized water, acetone), we were able to synthesize spherical Au and TiN nanoparticles of variable size between a few of nm and 30-40 nm under a relatively low size dispersion. EDX and XPS tests confirm that both nanoparticle samples consist of gold and titanium nitride in the absence of any impurity. While Au based nanoparticles demonstrate a standard plasmonic extinction peak in the visible green range (520-540 nm), TiN counterparts exhibit a broad red-shifted peak centered around 650-700 nm even for very small nanoparticle sizes (4-5 nm). We finally discuss possible applications of laser-synthesized Au nanoparticles in SERS, SEIRA and electrocatalysis, while TiN nanoparticles are considered as promising sensitizers of photothermal therapies.

2019, Kravets, V. G., Wu, F., Imaizumi, S., Grigorenko, A. N., Kabashin, A. V., Shipunova, V. O., Deyev, S. M., Кабашин, Андрей Викторович, Деев, Сергей Михайлович

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Light scattered by an object contains plethora information about the object which is distributed evenly among all possible Fourier components of light observed in the far-field. There are some cases, however, where this information is accumulated in the light confined by the object and then encoded in just a few coherent optical beams. Here, Fourier nanotransducers based on 2D plasmonic metamaterials are introduced, which are capable of confining light in 2D plane contacting with a functional interface, gathering information about its properties, and then transmitting the information into discrete optical beams with amplified phase relations. It is shown that phase of light in such beams can be used for probing dynamic physical properties of 2D materials and performing bio/chemical sensing with unprecedented sensitivity. Using a Fourier transducer based on periodic gold nanostructures, ferroelectric response from a single atomic layer of MoS 2 is resolved and studied for the first time, as well as the detection of important antibiotic chloramphenicol at fg mL −1 level is demonstrated, which several orders of magnitude better than reported in the literature. The implementation of phase-responsive Fourier nanotransducers opens new avenues in exploration of emergent 2D structures and radical improvement of biosensing technology.

2019, Lim, C. -K., Popov, A. A., Tselikov, G., Heo, J., Kabashin, A. V., Prasad, P. N., Кабашин, Андрей Викторович

Copyright © 2019 SPIE.Methods of femtosecond laser ablation in deionized water were used to fabricate ultrasmall (< 2 nm), bare (ligand-free) organic luminophore DCEtDCS nanoparticles, which exhibit aggregation enhanced emission in the green range (533 nm) with the quantum yield exceeding 58% and provide no concentration quenching. In contrast to chemically synthesized counterparts, laser-synthesized DCEtDCS nanoparticles do not contain any organic impurities due to their preparation in aqueous medium and do not require surfactants to stabilize colloidal solutions, which makes them highly suitable for intracellular uptake and bioimaging. The highly negative surface charge of these nanoparticles impeded their cellular uptake, but when the surface was coated with chitosan, a cationic polymer, intracellular uptake in microglia was achieved. Using in vitro model, we finally demonstrate the efficient employment of ultrasmall and surfactant free fluorescent organic nanoparticles prepared by laser ablation as markers in bioimaging.

2019, Singh, A., Swihart, M. T., Kabashin, A. V., Zavestovskaya, I. N., Prasad, P. N., Кабашин, Андрей Викторович, Завестовская, Ирина Николаевна

Copyright © 2019 American Chemical Society.This review describes promising laser-based approaches to produce silicon nanostructures, including laser ablation of solid Si targets in residual gases and liquids and laser pyrolysis of silane. These methods are different from, and complementary to, widely used porous silicon technology and alternative synthesis routes. One can use these methods to make stable colloidal dispersions of silicon nanoparticles in both organic and aqueous media, which are suitable for a multitude of applications across the important fields of energy and healthcare. Size tailoring allows production of Si quantum dots with efficient photoluminescence that can be tuned across a broad spectral range from the visible to near-IR by varying particle size and surface functionalization. These nanoparticles can also be integrated with other nanomaterials to make multifunctional composites incorporating magnetic and/or plasmonic components. In the energy domain, this review highlights applications to photovoltaics and photodetectors, nanostructured silicon anodes for lithium ion batteries, and hydrogen generation from water. Application to nanobiophotonics and nanomedicine profits from the excellent biocompatibility and biodegradability of nanosilicon. These applications encompass several types of bioimaging and various therapies, including photodynamic therapy, RF thermal therapy, and radiotherapy. The review concludes with a discussion of challenges and opportunities in the applications of laser-processed nanosilicon.

2020, Duflot, V., Popova-Kuznetsova, E., Tikhonowski, G., Popov, A. A., Deyev, S., Klimentov, S., Zavestovskaya, I., Prasad, P. N., Kabashin, A. V., Попова-Кузнецова, Елена Алефтиновна, Тихоновский, Глеб Валерьевич, Попов, Антон Александрович, Деев, Сергей Михайлович, Климентов, Сергей Михайлович, Завестовская, Ирина Николаевна, Кабашин, Андрей Викторович

© 2019 by the authors. Licensee MDPI, Basel, Switzerland.Nuclear nanomedicine is an emerging field, which utilizes nanoformulations of nuclear agents to increase their local concentration at targeted sites for a more effective nuclear therapy at a considerably reduced radiation dosage. This field needs the development of methods for controlled fabrication of nuclear agents carrying nanoparticles with low polydispersity and with high colloidal stability in aqueous dispersions. In this paper, we apply methods of femtosecond (fs) laser ablation in deionized water to fabricate stable aqueous dispersion of152Sm-enriched samarium oxide nanoparticles (NPs), which can capture neutrons to become153Sm beta-emitters for nuclear therapy. We show that direct ablation of a152Sm-enriched samarium oxide target leads to widely size-and shape-dispersed populations of NPs with low colloidal stability. However, by applying a second fs laser fragmentation step to the dispersion of initially formed colloids, we achieve full homogenization of NPs size characteristics, while keeping the same composition. We also demonstrate the possibility for wide-range tuning of the mean size of Sm-based NPs by varying laser energy during the ablation or fragmentation step. The final product presents dispersed solutions of samarium oxide NPs with relatively narrow size distribution, having spherical shape, a controlled mean size between 7 and 70 nm and high colloidal stability. The formed NPs can also be of importance for catalytic and biomedical applications.