Savinov, Maxim S

Chernyakova V.S., Tikhonovskii G.V., Satina A.P., Sozaev I.V., Savinov M.S., Shakhov P.V., Tselikov D.I., Popov A.A., Fronya A.A., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V.

The dimensional and optical properties of nanomaterials largely determine the prospects of their application in biomedicine. We have studied the feasibility of controlling the dimensional and optical characteristics of laser-synthesized titanium nitride (TiN) nanoparticles (NP) using various liquid media (water, isopropanol, acetone, or acetonitrile) and laser focusing parameters and energy. Laser ablation of the TiN target in all solvents resulted in the formation of spherical NPs with the mode and half-width of the size distribution dependent on the type of liquid. We show that the use of organic solvents can produce NPs with higher coefficients of mass extinction (up to 35.2 L cm–1 g–1) and of photothermal conversion (up to 69%) in the window of relative biotissue transparency for aqueous medium. It is also demonstrated that the mode and half-width of the TiN NP size distribution decreases as the distance from the lens to the target surface increases or laser radiation energy decreases. These findings form a quantitative basis for developing laser-synthesized TiN NPs with controlled properties and they also prove their high potential for applications in biomedicine.

Syuy A.V., Martynov I.V., Zavidovskiy I.A., Dyubo D.V., Sun Q., Yang X., Tikhonowski G.V., Tselikov D.I., Savinov M.S., Sozaev I., Popov A.A., Klimentov S.M., Tselikov G.I., Volkov V.S., Novikov S.M., et. al.

Abstract Dyes used in industries such as textile, paper, and leather are known to be harmful to both human health and aquatic ecosystems, which makes critically important the search of effective and sustainable methods for their removal from wastewater in order to mitigate the detrimental pollution effects. Here, we show that titanium nitride nanoparticles (TiN NPs) synthesized by scalable methods of pulsed laser ablation in liquid ambient (water, acetone and acetonitrile) can serve as extremely efficient sorbents for water decontamination from dye molecules (methylene blue, crystal violet, and malachite green). Our tests show that adsorption of TiN NPs is associated with the electrostatic effect due to a strong negative charge of laser-synthesized TiN NPs and the presence of pores in the NPs. Comprehensive characterization using scanning and transmission electron microscopy, along with Raman spectroscopy, evidenced that the appearance of surface charge is related to the formation of under-stoichiometric TiN (TiN1−x), associated with the predominance of nitrogen vacancies. This study identifies an optimal configuration of vacancy defects that maximizes dye adsorption, with TiN NPs synthesized in water exhibiting superior performance, achieving a dye sorption capacity of 136.5 mg g−1 at room temperature for methylene blue, which corresponds to best earlier reported values for nanomaterials. This study not only extends the utility of TiN NPs to environmental remediation but also highlights the critical influence of synthesis conditions on their functional properties, offering a pathway towards the design of more effective materials for pollution control.

Savinov M.S., Tikhonowski G.V., Pastukhov A.I., Fronya A.A., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V., Popov A.A.

The paper presents a study of the effect of the liquid medium type on the properties of zirconium nitride (ZrN) nanoparticles (NPs) synthesized by pulsed laser ablation in liquids (PLAL). A comparative analysis of the properties of NPs synthesized in six different liquids (acetonitrile, acetone, ethanol, isopropyl alcohol, dimethylformamide, and deionized water) demonstrates that NPs obtained in acetonitrile and acetone are the most promising for biomedical applications. Synthesized ZrN NPs can be used as sensitizers of innovative noninvasive methods of cancer therapy and contrast agents in diagnostics.

Sozaev I.V., Tikhonowski G.V., Savinov M.S., Popov A.A., Laktionov A.A., Kanavin A.P., Zavestovskaya I.N., Klimentov S.M., Pastukhov A.I., Kabashin A.V.

This paper presents a study of the dependence of the size and optical characteristics, as well as the productivity of laser synthesis of zirconium nitride (ZrN) nanoparticles (NPs) on laser ablation parameters. It is shown that changing the distance between the focusing lens and the target surface allows one to control the mode and half-width of the size distribution from (59 ± 35 nm) to (29 ± 14 nm), as well as spectrally shift the plasmon resonance peak from 638 nm to 680 nm. Additionally, a possibility of controlling the size characteristics of ZrN NPs when changing the laser radiation energy is demonstrated. Increasing the laser pulse energy from 10 to 100 μJ makes it possible to vary the NP size from (27 ± 13 nm) to (47 ± 30 nm). The results form a quantitative basis for the production of laser-synthesized ZrN NPs with controlled size and optical properties for applications in biomedicine.

Zavestovskaya I.N., Filimonova M.V., Popov A.L., Zelepukin I.V., Shemyakov A.E., Tikhonowski G.V., Savinov M., Filimonov A.S., Shitova A.A., Soldatova O.V., Kolmanovich D.D., Shakhov P.V., Kotelnikova P.A., Popov A.A., Chukavin N.N., et. al.

Proton therapy presents an appealing radiotherapy modality for the treatment of deeply-seated and unresectable tumors, but it still needs additional means to enhance the localization and efficiency of therapeutic action. Here we explore the use of elemental bismuth nanoparticles (Bi NPs) as sensitizers for proton therapy enhancement. Spherical Bi NPs were prepared by the method of pulsed laser ablation, followed by their coating with Pluronic polymer to stabilize them in a physiological environment. We observed efficient apoptotic cell death after proton irradiation at the Bragg peak, which was explained by high proton stopping power and low work function of Bi. The maximal effect was observed for 3 Gy radiation and 50 μg/mL NPs dose with 97 % inhibition of tumor cell clonogenic activity. The strong therapeutic effect was confirmed in vivo using aggressive Sa37 sarcoma tumors in mice. We observed 60 % inhibition of primary tumor growth with a decrease of metastatic potential in popliteal and axillary lymph nodes. Combined with X-ray contrast properties and radiosensitizing functionalities, the proposed concept of Bi NPs-enhanced proton therapy promises a major upgrade for cancer therapy.

Cheban M., Filatova S., Kravchenko Y., Scherbakov K., Mamonov D., Klimentov S., Savinov M., Chichkov M.

Filimonova M.V., Kolmanovich D.D., Tikhonowski G.V., Petrunya D.S., Kotelnikova P.A., Shitova A.A., Soldatova O.V., Filimonov A.S., Rybachuk V.A., Kosachenko A.O., Nikolaev K.A., Demyashkin G.A., Popov A.A., Savinov M.S., Popov A.L., et. al.

Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.

Lunyov I.V., Savinov M.S., Kabashin A.V., Popov A.A.

Savinov M.S., Griaznova O.Y., Tikhonowski G.V., Popov A.A., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V.

The possibility of using elemental bismuth nanoparticles as sensitizers for radiation therapy and computed tomography contrast agents is investigated. A comparative analysis of the X-ray contrast properties of bismuth nanoparticles with classical gold nanoparticles and bismuth oxychloride nanosheets is carried out. It is shown that laser-synthesized bismuth nanoparticles demonstrate higher X-ray contrast efficiency compared to traditional gold nanoparticles; they also have X-ray contrast properties similar to those of chemically synthesized analogues based on bismuth oxychloride nanosheets. Unique physicochemical characteristics in combination with high radiopaque properties of laser-synthesized bismuth nanoparticles form a new promising alternative to traditional sensitizers for radiation theranostics of oncological diseases.

Sozaev I.V., Tikhonowski G.V., Savinov M.S., Shakhov P.V., Skribitskaya A.V., Tselikov D.I., Popov A.A., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V.

The dependence of the efficiency of photothermal conversion of laser-synthesized bismuth (Bi) nanoparticles (NP) on size characteristics for applications in photothermal therapy is studied. It was shown that a decrease in the mode and half-width of the size distribution causes an increase in the photothermal conversion efficiency. Despite a decrease in the extinction in the relative transparency window of biological tissues (650–950 nm), Bi NPs of smaller sizes exhibit a more pronounced photothermal response caused by an increased contribution of absorption to the extinction. The unique combination of physicochemical properties of laser-synthesized Bi NPs forms a new promising alternative to conventional sensitizers of photothermal therapy of oncological diseases.

Smirnov N.A., Rupasov A.E., Shelygina S.N., Levchenko A.O., Savinov M.S., Kudryashov S.I.

In this work, we study the nonlinear absorption of ultrashort laser pulses of variable duration (0.3‒10 ps) in a bulk polycrystalline ZnSe dielectric. The transmission of the sample was measured for two wavelengths, 515 and 1030 nm, in a wide range of intensities. A nonlinear behavior of the transmission is found when the sample is irradiated with laser radiation at a wavelength of 515 nm with absorption saturation in the region of 3–5 TW/cm2. Surface damage thresholds were obtained for a wavelength of 1030 nm for pulse durations of 0.3–10 ps.

Zavestovskaya I.N., Popov A.L., Kolmanovich D.D., Tikhonowski G.V., Pastukhov A.I., Savinov M.S., Shakhov P.V., Babkova J.S., Popov A.A., Zelepukin I.V., Grigoryeva M.S., Shemyakov A.E., Klimentov S.M., Ryabov V.A., Prasad P.N., et. al.

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.

Savinov M.S., Tikhonowski G.V., Shakhov P.V., Kabashin A.V., Popov A.A.

Photoacoustic imaging (PAI) is a rapidly growing imaging modality, which combines high contrast of optical absorption with deep penetration depth of ultrasound. When combined with endogenous contrast agents based on light-absorbing nanoparticles (NPs), PAI can visualize various biological processes and tissues. Here, we describe a simple experimental setup based on a tissue-mimicking phantom with flexible optical properties for studying photoacoustic (PA) response of NPs. Our approach is based on a polyacrylamide gel phantom with independently variable optical absorption and scattering. The phantom allows one to model and study PA response of contrast agents with diverse spatial distributions and concentrations. To demonstrate high potential of the developed experimental setup, we prepared a phantom with optical properties matching human prostate tissue and performed a PAI of laser-synthesized titanium nitride (TiN) NPs, distributed in a disk-shaped area, located 10 mm under the phantom surface. We believe that our approach will contribute the successful development of clinical PAI with NPs-based contrast agents.

Kudryashov S.I., Savinov M.S., Levchenko A.O., Shelygina S.N., Rupasov A.E., Smirnov N.A.

In this work, we study the nonlinear absorption of ultrashort laser pulses of variable duration (0.3-10 ps) in a bulk polycrystalline ZnSe dielectric. The transmission of the sample was measured for two wavelengths, 515 and 1030 nm, in a wide range of intensities. A nonlinear behavior of the transmission is found when the sample is irradiated with laser radiation at a wavelength of 515 nm with absorption saturation in the region of 3-5 TW/cm2. Surface damage thresholds were obtained for a wavelength of 1030 nm for pulse durations of 0.3-10 ps. Keywords: nonlinear ZnSe absorption, solid-state immersion, two-photon absorption, chalcogenide glass surface ablation, ZnSe ablation thresholds.

Кудряшов С.И., Савинов М.С., Левченко А.О., Шелыгина С.Н., Рупасов А.Е., Смирнов Н.А.

In this work, we study the nonlinear absorption of ultrashort laser pulses of variable duration (0.3–10 ps) in a bulk polycrystalline ZnSe dielectric. The transmission of the sample was measured for two wavelengths, 515 and 1030 nm, in a wide range of intensities. A nonlinear behavior of the transmission is found when the sample is irradiated with laser radiation at a wavelength of 515 nm with absorption saturation in the region of 3–5 TW/cm2. Surface damage thresholds were obtained for a wavelength of 1030 nm for pulse durations of 0.3–10 ps.

Lv H., Hu B., Chen J., Li T., Peng C., Wang Y., Xue Y., Ma F., Yan Y., Tutu E.O.

Cheban M., Scherbakov K., Mamonov D., Parabin P., Filatova S., Kravchenko Y., Klimentov S., Chichkov M.

Wang L., Yang H., Zheng S., Fan X., Gao Q., Wang F., Chen Q., Liu P., Li L.

In this paper, high-purity zinc selenide (ZnSe) prepared by the Chemical Vapor Deposition (CVD) method was used as the raw material, and iron ion-doped zinc selenide polycrystals were successfully fabricated through the thermal diffusion method at 1100 °C for 30 h. The results showed that iron ions (Fe2+) successfully penetrated into the zinc selenide crystals, but the concentration of iron ions inside the crystals was relatively low, and the crystals exhibited numerous defects. To address this issue, we performed secondary sintering and annealing on the samples under high-temperature and high-pressure (HPHT) conditions, with the annealing temperature range set at 900–1200 °C. The results demonstrated that, under the synergistic effects of high temperature and high pressure, the lattice spacing in the crystals significantly decreased, defects were reduced, the distribution of iron ions became more uniform, and the concentration of iron ions in the central region increased. Additionally, the density and hardness of the samples were significantly improved. The method of secondary sintering under high-temperature and high-pressure provides a novel approach for the preparation of iron ion-doped zinc selenide polycrystalline ceramics, contributing to the enhancement of ceramic properties.

Albadr R.J., Taher W.M., Alwan M., Jawad M.J., Hiba Mushtaq, Yaseen B.M.

Abd El-Raheem H., Helim R., Hassan R.Y., Youssef A.F., Korri-Youssoufi H., Kraiya C.

Ma J., Shen H., Mi Z.

Proton therapy, characterized by its unique Bragg peak, offers the potential to optimize the destruction of cancer cells while sparing healthy tissues, positioning it as one of the most advanced cancer treatment modalities currently available. However, in comparison to heavy ions, protons exhibit a relatively lower relative biological effectiveness (RBE), which limits the efficacy of proton therapy. The incorporation of nanoparticles for radiosensitization presents a novel approach to enhance the RBE of protons. This review provides a comprehensive discussion of the recent advancements in augmenting the biological effects of proton therapy through the use of nanoparticles. It examines the various types of nanoparticles that have been the focus of extensive research, elucidates their mechanisms of radiation sensitization, and evaluates the factors influencing the efficiency of this sensitization process. Furthermore, this review discusses the latest synergistic therapeutic strategies that integrate nanoparticle-mediated radiosensitization and outlines prospective directions for the future application of nanoparticles in conjunction with proton therapy.

Filatova S.A., Kamynin V.A., Makeeva A.R., Rybaltovsky A.A., Fale A.E., Fedoseev A.I., Tsvetkov V.B.

A compact gain-switched all-fiber ytterbium laser operating at a wavelength of 1127 nm with the ability to control pulsed radiation parameters has been investigated. Gain switching was carried out by modulating the current of a semiconductor pump diode. With pumping energy ranging from 197.6 to 263.5 μJ, there was one generation pulse per each pump pulse with a duration of 0.43 to 1.1 μs, energy of 5.3 to 8.8 μJ, and a repetition rate of 100 Hz. Increasing the pumping energy above 265 μJ led to a change in the shape of generated pulses and to their energy rising up to 70 μJ.

Lv H., Gao J., Chen J., Li T., Peng C., Li Y., Ma F., Xue Y., Yan Y., Osei Tutu E.

Filimonova M.V., Kolmanovich D.D., Tikhonowski G.V., Petrunya D.S., Kotelnikova P.A., Shitova A.A., Soldatova O.V., Filimonov A.S., Rybachuk V.A., Kosachenko A.O., Nikolaev K.A., Demyashkin G.A., Popov A.A., Savinov M.S., Popov A.L., et. al.

Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.

Azarkin M., Kirakosyan M., Ryabov V.

Conventional X-ray therapy (XRT) is commonly applied to suppress cancerous tumors; however, it often inflicts collateral damage to nearby healthy tissue. In order to provide a better conformity of the dose distribution in the irradiated tumor, proton therapy (PT) is increasingly being used to treat solid tumors. Furthermore, radiosensitization with gold nanoparticles (GNPs) has been extensively studied to increase the therapeutic ratio. The mechanism of radiosensitization is assumed to be connected to an enhancement of the absorbed dose due to huge photoelectric cross-sections with gold. Nevertheless, numerous theoretical studies, mostly based on Monte Carlo (MC) simulations, did not provide a consistent and thorough picture of dose enhancement and, therefore, the radiosensitization effect. Radiosensitization by nanoparticles in PT is even less studied than in XRT. Therefore, we investigate the physics picture of GNP-enhanced RT using an MC simulation with Geant4 equipped with the most recent physics models, taking into account a wide range of physics processes relevant for realistic PT and XRT. Namely, we measured dose enhancement factors in the vicinity of GNP, with diameters ranging from 10 nm to 80 nm. The dose enhancement in the vicinity of GNP reaches high values for XRT, while it is very modest for PT. The macroscopic dose enhancement factors for realistic therapeutic GNP concentrations are rather low for all RT scenarios; therefore, other physico-chemical and biological mechanisms should be additionally invoked for an explanation of the radiosensitization effect observed in many experiments.

Savinov M.S., Tikhonowski G.V., Pastukhov A.I., Fronya A.A., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V., Popov A.A.

The paper presents a study of the effect of the liquid medium type on the properties of zirconium nitride (ZrN) nanoparticles (NPs) synthesized by pulsed laser ablation in liquids (PLAL). A comparative analysis of the properties of NPs synthesized in six different liquids (acetonitrile, acetone, ethanol, isopropyl alcohol, dimethylformamide, and deionized water) demonstrates that NPs obtained in acetonitrile and acetone are the most promising for biomedical applications. Synthesized ZrN NPs can be used as sensitizers of innovative noninvasive methods of cancer therapy and contrast agents in diagnostics.

Popov A.L., Kolmanovich D.D., Chukavin N.N., Zelepukin I.V., Tikhonowski G.V., Pastukhov A.I., Popov A.A., Shemyakov A.E., Klimentov S.M., Ryabov V.A., Deyev S.M., Zavestovskaya I.N., Kabashin A.V.

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.

Gu J., Su X., Li W., Xin M., Zhang D., Jin Y., Xu J., Guo B.

Damage to the substrate hinders the application of laser paint stripping (LPS) on carbon fiber reinforced polymers (CFRP), but the damage mechanism is currently unknown. In this paper, the LPS characteristics of CFRP, such as paint stripping depth, surface morphology and dynamic behavior, are firstly obtained. Subsequently, the surface damage mechanism of CFRP is discussed in detail by theoretical analysis and finite element method, and the effect of substrate damage on adhesive properties is investigated. The results show that it is difficult for LPS to obtain a complete surface free of paint residue. The strong laser plasma impact and resin pyrolysis pressure cause the resin to crack and flake before the paint is fully ablated. The carbon fiber then breaks and are thrown outward by heat and forces, and the surface with slightly fracture of the fiber will facilitate bonding with the paint.

Shah M.A., Firdous A., Dar G.N.

Radiation therapy mediated by nanoparticles is a new and exciting area in cancer treatment that offers creative ways to maximize the therapeutic benefit of radiation while reducing adverse effects. An overview of the most recent developments, difficulties, and opportunities in the quickly changing field of radiation therapy using nanoparticle-based techniques is given in this chapter. Using ionizing radiation to target and kill cancer cells, radiation therapy has long been a mainstay of cancer treatment. However, the small therapeutic window and sensitivity of the surrounding healthy tissues frequently pose problems for the effectiveness of standard radiation therapy. Because of their special physicochemical characteristics, nanoparticles offer a way to overcome these obstacles by enhancing the accuracy and selectivity of radiation delivery. Advancements in nanoparticle design and engineering have facilitated the development of agents capable of enhancing the effects of radiation on tumor cells. By using certain targeting moieties or passive mechanisms such as increased permeability and retention, these nanoparticles can be engineered to concentrate within tumor tissues in a targeted manner. Moreover, they can be designed to raise the amount of reactive oxygen species produced and amplify the absorption of ionizing radiation, which will raise the radiation’s therapeutic efficacy. Notwithstanding these encouraging advancements, obstacles still exist in the clinical application of radiation treatment mediated by nanoparticles. Biocompatibility, potential long-term toxicity, and pharmacokinetics need to be systematically addressed. Standardization of nanoparticle formulations, dosages, and administration protocols is crucial for ensuring the reproducibility and safety of these novel therapeutic strategies. Advancements in nanotechnology, imaging techniques, and our understanding of tumor biology will contribute to the refinement of nanoparticle designs for optimal therapeutic outcomes. Combining nanoparticle-based approaches with immunotherapy and other synergistic modalities may unlock new dimensions in cancer treatment, paving the way for personalized and multifaceted therapeutic interventions. Nanoparticle-mediated radiation therapy represents a paradigm shift in cancer treatment strategies. While challenges remain, the present chapter focuses on development in this field and its immense potential to revolutionize the landscape of radiation therapy, offering patients more effective and targeted treatments with reduced side effects.

Dell'Aglio M., De Giacomo A., Manno D., Mallardi A., Provenzano C., Marra M., Nocito F., Serra A., Quarta G., Paola Caricato A.

Boron nanoparticles (BNPs) are attractive nanomaterials for their employment in many applications, such as neutron detection, boron neutron capture therapy, proton boron capture therapy and nuclear fusion. Depending on the specific application, 10B or 11B isotopes can be used. Nevertheless, there are significant challenges in developing suitable BNPs using both conventional chemical synthesis routes and dry fabrication techniques. In this study we report BNPs directly synthetised in water by pulsed Laser Ablation in Liquid (PLAL). Nanoparticles of elemental boron have been generated by laser ablation of a sintered 10B target in MilliQ water by employing ns laser pulse. The ablation resulted in BNPs and boron target micro-fragments with hydrogen gas and boric acid as by-products. Simple washing steps were used to obtain clean BNPs in water. The BNPs showed a narrow size distribution between 3 and 4 nm and their stability in water was induced by a thin layer of boron oxide surrounds BNPs. The BNPs were fully characterized by the chemical and structural point of view employing several techniques. A discussion on boron chemical reactions during laser ablation in water and after the NPs were released in solution was done.

Zelepukin I.V., Shevchenko K.G., Deyev S.M.

AbstractRapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier – the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method.

Bahamondes Lorca V.A., Ávalos-Ovando O., Sikeler C., Ijäs H., Santiago E.Y., Skelton E., Wang Y., Yang R., Cimatu K.L., Baturina O., Wang Z., Liu J., Slocik J.M., Wu S., Ma D., et. al.

Yang C., Zhang B., Lin X., Han Q., Bao H., Liu Y.

Concentration plays an essential role in generating hydroxyl radicals in irradiated nanoenhancer suspensions. In this paper, we used coumarin-3-carboxylic acid as a hydroxyl radical-specific probe to investigate the hydroxyl radical production of different concentration nanodiamonds (NDs) and CeO2 NPs in phosphate-buffered saline under x-ray irradiation. NDs significantly enhanced hydroxyl radical production, and the maximum enhancement of hydroxyl radical production was observed at a concentration of 10 µg/ml, with an enhanced factor of 1.398 ± 0.262. CeO2 NPs can increase and scavenge hydroxyl radicals at different concentration ranges, with the lowest and highest enhanced factors of 0.623 ± 0.069 and 1.738 ± 0.264, respectively. We tested the hydrodynamic diameter at various concentrations to explore the concentration effect further. We found that with increasing concentration, there might be factors, such as hydroxyl radical recombination and nanoparticle agglomeration, that lead to changes in the enhancement factor. Based on the data from previous and present studies, the experimental results indicate that the concentration factor is essential for hydroxyl radical generation in nanoenhancer suspensions under ionizing radiation. We also provide possible mechanisms for enhancing hydroxyl radical production by nanoenhancers in water under ionizing radiation and the decrease in enhancement factor at high concentrations of nanoenhancers.

Tahir, Concas G.C., Gisbert M., Cremona M., Lazaro F., Maia da Costa M.E., De Barros S.D., Aucélio R.Q., Pierre T.S., Godoy J.M., Mendes D., Mariotto G., Daldosso N., Enrichi F., Cuin A., et. al.

Over the last decade, the CO2 reduction reaction (CO2RR) has been increasingly exploited for the synthesis of high‐value raw materials in gaseous or liquid form, although no examples of CO2 fixation in nanoparticle systems have been demonstrated. Herein, CO2 fixation into solid nanomaterials by laser synthesis and processing of gold colloids in water, traditionally considered a green approach leading to ligand‐free nanoparticles without the formation of by‐products, is reported. If carbon monoxide‐rich gold nanoparticles are observable even after synthesis in deionized water, the presence of CO2 derivatives in alkaline water environment leads to C2 and C3 coupling with the production of carboxylic acids as a typical CO2RR fingerprint. While laser processing of preformed gold colloids is selective for C2 coupling, both C2 and C3 coupling to lactic acid are observed during pulsed laser ablation of a gold target. In the latter case, it is demonstrated that it is possible to synthesize photoluminescent organometallic nanocomposites in the blue spectral region with a quantum yield of about 20% under adequate experimental conditions. In this research, new pathways are offered to be explored in energetics, photonics, catalysis, and synthesis at the nanoscale.

Belyaev I.B., Zelepukin I.V., Kotelnikova P.A., Tikhonowski G.V., Popov A.A., Kapitannikova A.Y., Barman J., Kopylov A.N., Bratashov D.N., Prikhozhdenko E.S., Kabashin A.V., Deyev S.M., Zvyagin A.V.

AbstractBiodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond‐laser ablation in liquids rapidly dissolve in physiological‐like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half‐life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near‐infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9‐fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass‐extinction of Ge NPs (7.9 L g−1 cm−1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near‐infrared‐light biodegradable Ge nanomaterial holds promise for advanced theranostics.

Lin H., Buerki-Thurnherr T., Kaur J., Wick P., Pelin M., Tubaro A., Carniel F.C., Tretiach M., Flahaut E., Iglesias D., Vázquez E., Cellot G., Ballerini L., Castagnola V., Benfenati F., et. al.

Ivanov D.S., Shakhov P., Tikhonowsky G., Popov A.A., Mayorov A.N., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V.

Pulsed Laser Ablation in Liquids (PLAL) manifested itself as a powerful tool for the synthesis of nanoparticles (NPs) from a variety of materials of high demand in biomedicine. The mechanisms and regimes of nanostructures formation, however, still require clarification in order to better control the final NPs characteristics. Here, we present a numerical study of femtosecond laser-ablative production of metal (gold) NPs in water ambient using an advanced atomistic continuum approach, combining the Molecular Dynamics (MD) and Two Temperature Model into the frames of a single MD-TTM computational method. The model describes non-equilibrium laser-induced phase transitions at atomic level and accounts for the effect of free carriers in continuum. With the MD-TTM model we investigated the effect of slight porosity arising due to a partial overlap of laser craters during the scanning of laser beam over the target surface under a high repetition rate of laser pulses. For that purpose, we perform a simulation of 270 fs laser pulse interaction with solid and porous gold targets at the incident fluence of 2.5 J/cm2. The obtained results revealed the manifestation of different regimes of ablation and different yield of the obtained NPs. The simulation results are compared with the corresponding experimental data. We found that depending on the scanning speed the ablation can follow thermal and spallation mechanisms of the material ejection, which are responsible for the appearance of fine and course populations of NPs correspondingly. In the case of clean target’s surface ablation, when at high scanning speed of 3840 mm/s each pulse hits a fresh area, the material ejection is governed by both mechanisms, which leads to the appearance of bimodal population of NPs. Alternatively, a moderate scanning speed of 840 mm/s results in a partial overlap of the sequential laser spots on the surface and generated slight porosity removes the accumulation of laser-induced stresses. The spallation mechanism of the material ejection is therefore suppressed, which results in generation of a monomodal fine population of NPs with a 20 times larger yield. The obtained data are of importance to predict and control size characteristics of laser-synthesized nanomaterials.

Zavestovskaya I.N., Kasatova A.I., Kasatov D.A., Babkova J.S., Zelepukin I.V., Kuzmina K.S., Tikhonowski G.V., Pastukhov A.I., Aiyyzhy K.O., Barmina E.V., Popov A.A., Razumov I.A., Zavjalov E.L., Grigoryeva M.S., Klimentov S.M., et. al.

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a 10B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles.

Biliak K., Protsak M., Pleskunov P., Nikitin D., Hanuš J., Ali-Ogly S., Šomvársky J., Tosca M., Cieslar M., Košutová T., Dopita M., Lopes Ferreira F., Choukourov A.

Savinov M.S., Griaznova O.Y., Tikhonowski G.V., Popov A.A., Zavestovskaya I.N., Klimentov S.M., Kabashin A.V.

The possibility of using elemental bismuth nanoparticles as sensitizers for radiation therapy and computed tomography contrast agents is investigated. A comparative analysis of the X-ray contrast properties of bismuth nanoparticles with classical gold nanoparticles and bismuth oxychloride nanosheets is carried out. It is shown that laser-synthesized bismuth nanoparticles demonstrate higher X-ray contrast efficiency compared to traditional gold nanoparticles; they also have X-ray contrast properties similar to those of chemically synthesized analogues based on bismuth oxychloride nanosheets. Unique physicochemical characteristics in combination with high radiopaque properties of laser-synthesized bismuth nanoparticles form a new promising alternative to traditional sensitizers for radiation theranostics of oncological diseases.

Obayomi K.S., Lau S.Y., Danquah M.K., Zhang J., Chiong T., Meunier L., Gray S.R., Rahman M.M.

Water-soluble dyes are a common problem in wastewater treatment, requiring highly efficient methods for removal. In this study, novel sustainable adsorbents made from graphene-oxide (GO) and other materials, such as eggshell-derived calcium oxide nanoparticles (CaONPs-ES), fish bone calcium oxide nanoparticles (CaONPs-FB), and durian shell activated carbon (DSAC) were synthesized, characterized, and demonstrated for soluble dye removal from wastewater. Fermented maize grain extract (MES) was used as a green cross-linker in the synthesis process. The resulting nanocomposites, [email protected]/DSAC and [email protected]/DSAC, showed promising adsorption capabilities for methylene blue (MB) dye removal from aqueous environments. The prepared nanocomposites ([email protected]/DSAC and [email protected]/DSAC) were characterize using state-of-art instrumental techniques. The BET measurement revealed that the nanocomposites surface areas were enhanced due to the cross-linking phenomenon, improving their adsorption capability towards MB dye treatment. The adsorption data of [email protected]/DSAC and [email protected]/DSAC was well fitted to the Harkins-Jura and Freundlich models, respectively. The maximum sorption capacities of [email protected]/DSAC and [email protected]/DSAC were 1274.5 and 689.7 mg/g, respectively. The MB dye removal mechanism was driven by π-π interaction, hydrogen bonding, electrostatic attraction and physical interactions and the adsorption process of the nanocomposites followed pseudo-second-order kinetics. The adsorptive performance of the nanocomposites was stable, showing ~96.45 % and ~85.18 % after 10 successive cycles for [email protected]/DSAC and [email protected]/DSAC respectively. Cost evaluation revealed that bulk synthesis of [email protected]/DSAC and [email protected]/DSAC nanocomposites is cost-effective for treating large quantities of MB contaminated water and other potential dyes as well. Finally, the independent and synergetic contributions between pH, adsorbent dosage and temperature on MB removal by [email protected]/DSAC and [email protected]/DSAC were studied and optimized by central composite design (CCD) an aspect of the response surface methodology (RSM). Finally, this study suggests that the novel green cross-linking approach has a significant impact in enhancing the adsorptive performances of the developed nanocomposites to effectively capture MB from aqueous environment.

Johny J., van Halteren C.E., Cakir F., Zwiehoff S., Behrends C., Bäumer C., Timmermann B., Rauschenbach L., Tippelt S., Scheffler B., Schramm A., Rehbock C., Barcikowski S.

AbstractGold nanoparticles (AuNPs) are currently the most studied radiosensitizers in proton therapy (PT) applicable for the treatment of solid tumors, where they amplify production of reactive oxygen species (ROS). However, it is underexplored how this amplification is correlated with the AuNPs’ surface chemistry. To clarify this issue, we fabricated ligand‐free AuNPs of different mean diameters by laser ablation in liquids (LAL) and laser fragmentation in liquids (LFL) and irradiated them with clinically relevant proton fields by using water phantoms. ROS generation was monitored by the fluorescent dye 7‐OH‐coumarin. Our findings reveal an enhancement of ROS production driven by I) increased total particle surface area, II) utilization of ligand‐free AuNPs avoiding sodium citrate as a radical quencher ligands, and III) a higher density of structural defects generated by LFL synthesis, indicated by surface charge density. Based on these findings it may be concluded that the surface chemistry is a major and underexplored contributor to ROS generation and sensitizing effects of AuNPs in PT. We further highlight the applicability of AuNPs in vitro in human medulloblastoma cells.

Zavestovskaya I.N., Popov A.L., Kolmanovich D.D., Tikhonowski G.V., Pastukhov A.I., Savinov M.S., Shakhov P.V., Babkova J.S., Popov A.A., Zelepukin I.V., Grigoryeva M.S., Shemyakov A.E., Klimentov S.M., Ryabov V.A., Prasad P.N., et. al.

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.

Hendrix Y., Rauwel E., Nagpal K., Haddad R., Estephan E., Boissière C., Rauwel P.

ZnO is an effective photocatalyst applied to the degradation of organic dyes in aqueous media. In this study, the UV-light and sunlight-driven photocatalytic activities of ZnO nanoparticles are evaluated. A handheld Lovibond photometer was purposefully calibrated in order to monitor the dye removal in outdoor conditions. The effect of ZnO defect states, i.e., the presence of zinc and oxygen defects on the photocatalytic activity was probed for two types of dyes: fuchsin and methylene blue. Three morphologies of ZnO nanoparticles were deliberately selected, i.e., spherical, facetted and a mix of spherical and facetted, ascertained via transmission electron microscopy. Aqueous and non-aqueous sol-gel routes were applied to their synthesis in order to tailor their size, morphology and defect states. Raman spectroscopy demonstrated that the spherical nanoparticles contained a high amount of oxygen vacancies and zinc interstitials. Photoluminescence spectroscopy revealed that the facetted nanoparticles harbored zinc vacancies in addition to oxygen vacancies. A mechanism for dye degradation based on the possible surface defects in facetted nanoparticles is proposed in this work. The reusability of these nanoparticles for five cycles of dye degradation was also analyzed. More specifically, facetted ZnO nanoparticles tend to exhibit higher efficiencies and reusability than spherical nanoparticles.

Lo C., Tsai S., Niu H., Chen F., Hwang H., Chao T., Hsiao I., Liaw J.