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High resolution electron microscopy images of laser-synthesized NPs: (a) Typical TEM image (inset) and corresponding size distribution of as-prepared boron-based NPs. (b) Typical TEM image (inset) and corresponding size distribution of boron NPs after multiple centrifugation and purification steps. (c) Typical EDX map of NPs prepared by fs laser ablation in water. Cyan color corresponds to boron. (d) HR-TEM image of a polycrystalline nanostructure.
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Boron-based nano-formulations look very promising for biomedical applications, including photo- and boron neutron capture therapies, but the fabrication of non-toxic water-dispersible boron nanoparticles (NPs), which contain the highest boron atom concentration, is difficult using currently available chemical and plasma synthesis methods. Here, we...
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... (650-900 nm), which is in agreement with previously reported optical extinction data for elemental boron NPs 17 , suggesting the possibility of NPs applications in photoacoustic imaging photothermal therapy. Our tests using transmission electron microscopy (TEM) showed that the prepared solutions were mainly composed of spherical NPs (inset in Fig. 2a), while their averaged (mode) diameter was 37 nm (Fig. 2a), as followed from our statistical analysis. According to Energy-dispersive X-ray spectroscopy (EDX) analysis, the formed nanostructures contained a significant amount of boron detected in regions where high contrast NPs were located (Fig. 2c), suggesting the domination of this ...Context 2
... optical extinction data for elemental boron NPs 17 , suggesting the possibility of NPs applications in photoacoustic imaging photothermal therapy. Our tests using transmission electron microscopy (TEM) showed that the prepared solutions were mainly composed of spherical NPs (inset in Fig. 2a), while their averaged (mode) diameter was 37 nm (Fig. 2a), as followed from our statistical analysis. According to Energy-dispersive X-ray spectroscopy (EDX) analysis, the formed nanostructures contained a significant amount of boron detected in regions where high contrast NPs were located (Fig. 2c), suggesting the domination of this element in the nanoparticle composition. In addition, ...Context 3
... were mainly composed of spherical NPs (inset in Fig. 2a), while their averaged (mode) diameter was 37 nm (Fig. 2a), as followed from our statistical analysis. According to Energy-dispersive X-ray spectroscopy (EDX) analysis, the formed nanostructures contained a significant amount of boron detected in regions where high contrast NPs were located (Fig. 2c), suggesting the domination of this element in the nanoparticle composition. In addition, examining TEM images, we could observe a lower contrast shell coating of NPs and elongated interconnections between the adjacent NPs (Fig. 2a). The presence of such low-contrast structures is consistent with the formation of boron-related compounds ...Context 4
... nanostructures contained a significant amount of boron detected in regions where high contrast NPs were located (Fig. 2c), suggesting the domination of this element in the nanoparticle composition. In addition, examining TEM images, we could observe a lower contrast shell coating of NPs and elongated interconnections between the adjacent NPs (Fig. 2a). The presence of such low-contrast structures is consistent with the formation of boron-related compounds (boric acid, boron oxide) crystallized on the surface after drying of NPs on a TEM grid. To clarify the origin of these structures, we separated the NPs from the solution by centrifugation www.nature.com/scientificreports/ with ...Context 5
... by-product of synthesis, we applied a purification procedure based on multiple centrifugation steps in order to extract the remaining boron-based nanoformulations in pure state. Then, we washed them with deionized water to remove the excess of the boric acid residues. A typical TEM image of boron NPs after the purification step is shown in Fig. 2b. One can see that the NPs were ideally spherical, while the characteristic low-contrast shell coatings and interconnections between adjacent NPs were absent, suggesting that these structures were indeed related to boric acid and then washed out during the purification. As shown in Fig. 2b, the averaged size of NPs (~ 40 nm) was nearly ...Context 6
... image of boron NPs after the purification step is shown in Fig. 2b. One can see that the NPs were ideally spherical, while the characteristic low-contrast shell coatings and interconnections between adjacent NPs were absent, suggesting that these structures were indeed related to boric acid and then washed out during the purification. As shown in Fig. 2b, the averaged size of NPs (~ 40 nm) was nearly identical to the size of NPs before purification. It should be noted that in addition to relatively small NPs (tens of nm) forming the majority of nanoparticle population, we observed a certain number of larger NPs (several hundreds of nm). Since we mainly focused our attention on the ...Context 7
... believe that the appearance of BN features is an artifact related to catalytic activity of boron NPs under partial nitrogen exposure during their preparation of samples in atmospheric air 42,43 . The supposition of certain extent of crystallinity of small boron NPs was confirmed by the analysis of high-resolution TEM (HR-TEM) images. As shown in Fig. 2d polycrystalline structure is clearly resolvable despite a significant presence of the amorphous phase. The calculated interplanar spacing is 4.46 Å, which corresponds to the (113) plane of the elemental β-boron, suggesting the presence of a substantial fraction of crystalline boron in the nanoparticle composition. ...Context 8
... and 191.2 eV, evidencing the formation of boron nitride-based 48 and boron carbide-based (boronic acid groups) 49-51 compounds on the nanoparticle surface. The production of carbide-based residues can be due to contamination of the boron target with carbon, whereas the formation of boron nitride was unexpected. The XPS survey of such samples (Fig. S2a) confirms the presence of a peak in N 1 s region. We believe that the formation of nitrogen-related compounds on the surface of NPs can be explained by the exposure of samples to ambient air during sample preparation and drying steps, which led to catalytic reaction with ...Context 9
... /n boric acid = 2.45, as reported by ICP-MS. However, the difference in structural properties of boron NPs prepared by both methods was not substantial, as it took place in the case of Si nanoparticles 32 . Indeed, TEM analysis did not reveal any significant deviation of the averaged diameter of NPs prepared in degassed and non-degassed samples (Figs. S3 and 2b, respectively) while XRD (not shown for degassed NPs) and XPS (Figs. S4 and 4, respectively) evidenced similar properties of NPs prepared by both methods. It should be noted that similarly to the non-degassed case, we recorded boron nitride-related peak in XPS spectrum of NPs prepared in Ar-bubbled ambient (Figs. S4 and S2b). This fact ...Context 10
... non-degassed samples (Figs. S3 and 2b, respectively) while XRD (not shown for degassed NPs) and XPS (Figs. S4 and 4, respectively) evidenced similar properties of NPs prepared by both methods. It should be noted that similarly to the non-degassed case, we recorded boron nitride-related peak in XPS spectrum of NPs prepared in Ar-bubbled ambient (Figs. S4 and S2b). This fact supports our supposition on the appearance of this signal as a result of catalytic activity of boron during post-fabrication exposition of samples to air. Indeed, since Ar-bubbled water is free of nitrogen, there is no N 2 source to produce BN compounds. As a conclusion from these tests, the minimization of oxygen content ...Citations
... Such a technique can provide a series of advantages, including the cleanness of nanomaterials (e.g., it can be performed in deionized water or organic solutions), and natural liquid dispersibility in the absence of aggregation effects due to the formation of NPs in a liquid environment. We recently demonstrated the efficient synthesis of boron-containing nanoformulations, including Fe 2 B NPs [42] and elemental boron NPs (BNPs) [43,44], using PLAL methods. The ablation by long (nanosecond) laser radiation in organic solutions typically leads to the formation of partially carbonized amorphous boron NPs (a-BNPs) of small size (10-30 nm) [43], while ultrashort (femtosecond) laser ablation in deionized water could result in the formation of partially crystalline elemental BNPs (pc-BNPs) of slightly larger size (30-50 nm) and boric acid as a byproduct, which could be later removed by centrifugation [44]. ...
... We recently demonstrated the efficient synthesis of boron-containing nanoformulations, including Fe 2 B NPs [42] and elemental boron NPs (BNPs) [43,44], using PLAL methods. The ablation by long (nanosecond) laser radiation in organic solutions typically leads to the formation of partially carbonized amorphous boron NPs (a-BNPs) of small size (10-30 nm) [43], while ultrashort (femtosecond) laser ablation in deionized water could result in the formation of partially crystalline elemental BNPs (pc-BNPs) of slightly larger size (30-50 nm) and boric acid as a byproduct, which could be later removed by centrifugation [44]. We also showed that laser-synthesized BNPs represent promising sensitizers of photothermal therapy under IR irradiation [45], which could be enabled in parallel with a radiotherapy channel to increase therapeutic outcomes. ...
... Briefly, a-BNPs were synthesized by the ablation of a pure boron micropowder by 200 ns laser radiation at the wavelength of 1060-1070 nm in isopropanol, followed by the laser fragmentation of the formed solution. For the formation of pc-BNPs, we used a technique of ultrashort (270 fs) laser ablation from a bulk boron target in deionized water, similar to our previous work [44]. In both cases, PLAL led to fast coloration of the liquid in the ablation chamber, indicating NP formation. ...
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.
... Nanomaterials synthesized by PLAL methods have shown high efficiency in nanophotonics, catalysis, energy and biomedicine [18][19][20][21][22]. Methods of femtosecond laser ablation have proven to be particularly effective in terms of controlling the size and composition of NPs [16,17]. Using these methods, we have recently synthesized a whole series of new NMs, including monoelemental and multicomponent metal NPs [9,[23][24][25][26][27], semiconductors [28][29][30], and nanocomposites [31,32]. ...
... Based on a natural formation of nanoclusters during the action of laser radiation on a solid target, PLAL profits from clean and essentially non-equilibrium conditions of nanostructure growth, which makes the formation of non-toxic complex multi-component nanoformulations possible [27]. As we have shown in previous studies, owing to the much lower amount of energy required to ablate a unity of material, femtosecond (fs) laser ablation is especially efficient in controlling the size characteristics of formed nanomaterials, from single spherical NPs [28][29][30] to complex multi-functional core-satellite or core-shell nanoarchitectures [31][32][33]. The choice of this technique for the engineering of Si-Fe nanoformulations is justified by specific nanofabrication conditions: (i) the easy preparation of different compositions of NPs, which can be obtained only in the form of colloidal solutions; (ii) the nearly spherical shape of Si-Fe NPs (iii) the inherent stability of prepared colloidal solutions of bare (ligand-free) NPs and (iv) the possibility of the minimization of residual toxic by-products. ...
The combination of photothermal and magnetic functionalities in one biocompatible nanoformulation forms an attractive basis for developing multifunctional agents for biomedical theranostics. Here, we report the fabrication of silicon–iron (Si-Fe) composite nanoparticles (NPs) for theranostic applications by using a method of femtosecond laser ablation in acetone from a mixed target combining silicon and iron. The NPs were then transferred to water for subsequent biological use. From structural analyses, it was shown that the formed Si-Fe NPs have a spherical shape and sizes ranging from 5 to 150 nm, with the presence of two characteristic maxima around 20 nm and 90 nm in the size distribution. They are mostly composed of silicon with the presence of a significant iron silicide content and iron oxide inclusions. Our studies also show that the NPs exhibit magnetic properties due to the presence of iron ions in their composition, which makes the formation of contrast in magnetic resonance imaging (MRI) possible, as it is verified by magnetic resonance relaxometry at the proton resonance frequency. In addition, the Si-Fe NPs are characterized by strong optical absorption in the window of relative transparency of bio-tissue (650–950 nm). Benefiting from such absorption, the Si-Fe NPs provide strong photoheating in their aqueous suspensions under continuous wave laser excitation at 808 nm. The NP-induced photoheating is described by a photothermal conversion efficiency of 33–42%, which is approximately 3.0–3.3 times larger than that for pure laser-synthesized Si NPs, and it is explained by the presence of iron silicide in the NP composition. Combining the strong photothermal effect and MRI functionality, the synthesized Si-Fe NPs promise a major advancement of modalities for cancer theranostics, including MRI-guided photothermal therapy and surgery.
... To solve these problems during the preparation of B NPs, we recently proposed to employ the technique of femtosecond (fs) laser ablation in liquids, which was earlier successfully used in the synthesis of a variety of nanomaterials, including metal/semimetal [33][34][35] and semiconductor [36][37][38] NPs. Here, a crystalline B target submerged in deionized water was ablated by focused fs laser irradiation, resulting in the formation of aqueous solutions of colloidal NPs and boric acid as a by-product, which could be easily removed by centrifugation [39]. The advantage of this method consists of the cleanness of the synthesis and natural water dispersity of formed nanoparticles. ...
... The advantage of this method consists of the cleanness of the synthesis and natural water dispersity of formed nanoparticles. Furthermore, we showed that laser-synthesized B NPs have a very low toxicity profile and can be used as sensitizers in photothermal therapy as an attractive additional modality, which could be enabled in parallel with the radiotherapy channel [39,40]. ...
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.
... As such, drug-based particles generated by laser ablation offer the same advantages as carrier-assisted drug delivery systems, including improved drug stability and biocompatibility [50][51][52] , while also minimizing the risk of carrier induced toxicity 50,52 and having greater potential for higher drug loading capacities 50,51 . In addition, laser ablation allows for size control by modulating the laser power and pulse width [53][54][55][56] , ablation time duration 57 , and through the use of stabilizing surfactants 41,58,59 . Furthermore, as organic solvents used for chemical synthesis of nanoparticles are not needed in laser ablation, which we conduct in an aqueous environment, this method is considered a "green" biocompatible method of nanoparticle synthesis [41][42][43] . ...
Nanomedicine offers a number of innovative strategies to address major public health burdens, including influenza and SARS-CoV-2. In this work, we introduce a multi-drug nanoparticle fabricated using femtosecond laser ablation which can be used for the treatment of influenza, SARS-CoV-2, and their co-infections. The influenza antiviral, baloxavir marboxil; the SARS-CoV-2 antiviral, remdesivir; and the anti-inflammatory drug, dexamethasone, were co-ablated in aqueous media, followed by surface modification with a cationic polymer to generate a nanoparticle with a diameter of ~73 nm and a positive zeta potential. We demonstrate high efficacy of these nanoparticles against Influenza Virus A using a clinically relevant, in vitro primary mouse trachea epithelial cell-air-liquid interface culture model. These findings demonstrate great promise both for the use of femtosecond laser ablation to generate multi-drug nanoparticles, as well as for the potential anti-viral effects of our nanoformulation against other respiratory virus infections such as SARS-CoV-2.
... Moreover, this nanomaterial is very biocompatible, especially when its colloidal solutions are synthesized without using of potentially toxic chemical compounds. In particular, we recently introduced new laser-synthesized colloidal solutions of bare TiN NPs and a variety of other NPs [22][23][24][25] . and demonstrated their good biocompatibility both in vivo and in vitro as well as high photothermal effect in vitro even at very low concentrations 20,26,27 . ...
... In [16], Pastukhov et al. reported the formation of aqueous solutions of elemental crystalline BNPs with the averaged modal size of about 37 nm for biomedical applications using fs laser beams (1025 nm, 480 fs, 8 kHz, or 1030 nm, 270 fs) focused on a hot-pressed 99.5%, natural isotopic boron target. ...
... The plasma emission was finally employed both to identify the sample elements and to perform quantitative analysis by optical emission spectroscopy. It is known that ablation of boron target also induces the formation of boric acid as by-product [16] that can bias the quantification of BNPs by LIBS. In order to avoid a BNPs overestimation, a washing procedure of synthesized BNPs based on three ultracentrifugation steps was performed in order to obtain BNPs redispersed in a pure water solution. ...
... By the inspection of the figure, we can see that while the air peak is very similar, demonstrating we sampled the same amount of gas, the H 2 peak is present only in the PLAL experiment with B, while in the case of Au the peak is absent or at least negligible. The formation of the boric hydroxyl, from one hand passivates the particle surface and prevents the complete dissolution of the particle [16] with the formation of boric acid and, from the other hand stabilizes the particle. ...
... By introducing some nerve agents into the liquid, single and multi-drug hybrid nanoparticles can be achieved. Nanoparticles, such as gold (Bailly et al., 2019), silicon (Petriev et al., 2019), titanium nitride (Zelepukin et al., 2021;Aa et al., 2022), and boron (Pastukhov et al., 2022), are often chosen as nano drug carriers or photothermal therapy agents for neurological diseases. ...
As a typical micro/nano processing technique, femtosecond laser fabrication provides the opportunity to achieve delicate microstructures. The outstanding advantages, including nanoscale feature size and 3D architecting, can bridge the gap between the complexity of the central nervous system in virto and in vivo. Up to now, various types of microstructures made by femtosecond laser are widely used in the field of neurobiological research. In this mini review, we present the recent advancement of femtosecond laser fabrication and its emerging applications in neurobiology. Typical structures are sorted out from nano, submicron to micron scale, including nanoparticles, micro/nano-actuators, and 3D scaffolds. Then, several functional units applied in neurobiological fields are summarized, such as central nervous system drug carriers, micro/nano robots and cell/tissue scaffolds. Finally, the current challenges and future perspective of integrated neurobiology research platform are discussed.
