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Abstract Biodegradable 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.

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.

Abstract 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 demonstrate purely aqueous synthesis of clean boron NPs by methods of femtosecond laser ablation from a solid boron target in water, thus free of any toxic organic solvents, and characterize their properties. We show that despite highly oxidizing water ambience, the laser-ablative synthesis process follows an unusual scenario leading to the formation of boron NPs together with boric acid (H3BO3) as an oxidation by-product coating the nanoparticles, which acts to stabilize the elemental boron NPs dispersion. We then demonstrate the purification of boron NPs from residual boric acid in deionized water, followed by their coating with polyethylene glycol to improve colloidal stability and biocompatibility. It was found that the formed NPs have a spherical shape with averaged size of about 37 nm, and are composed of elemental boron in mostly amorphous phase with the presence of certain crystalline fraction. The synthesized NPs demonstrate low toxicity and exhibit strong absorption in the NIR window of relative tissue transparency, promising their use in photoacoustic imaging and phototherapy, in addition to their promise for neutron capture therapy. This combined potential ability of generating imaging and therapy functionalities makes laser-synthesized B NPs a very promising multifunctional agent for biomedical applications.

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.

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.

Abstract 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.

Owing to a strong photothermal response in the near-IR spectral range and very low toxicity, titanium nitride (TiN) nanoparticles (NPs) synthesized by pulsed laser ablation in liquids (PLAL) present a novel appealing object for photo-induced therapy of cancer, but the properties of these NPs still require detailed investigation. Here, we have elaborated methods of femtosecond laser ablation from the TiN target in a variety of liquid solutions, including acetonitrile, dimethylformamide, acetone, water, and H2O2, to synthesize TiN NPs and clarify the effect of liquid type on the composition and properties of the formed NPs. The ablation in all solvents led to the formation of spherical NPs with a mean size depending on the liquid type, while the composition of the NPs ranged from partly oxidized TiN to almost pure TiO2, which conditioned variations of plasmonic peak in the region of relative tissue transparency (670–700 nm). The degree of NP oxidation depended on the solvent, with much stronger oxidation for NPs prepared in aqueous solutions (especially in H2O2), while the ablation in organic solvents resulted in a partial formation of titanium carbides as by-products. The obtained results contribute to better understanding of the processes in reactive PLAL and can be used to design TiN NPs with desired properties for biomedical applications.

Hybrid multimodal nanoparticles, applicable simultaneously to the noninvasive imaging and therapeutic treatment, are highly demanded for clinical use. Here, Fe-Au core-satellite nanoparticles prepared by the method of pulsed laser ablation in liquids were evaluated as dual magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and as sensitizers for laser-induced hyperthermia of cancer cells. The biocompatibility of Fe-Au nanoparticles was improved by coating with polyacrylic acid, which provided excellent colloidal stability of nanoparticles with highly negative ζ-potential in water (−38 ± 7 mV) and retained hydrodynamic size (88 ± 20 nm) in a physiological environment. The ferromagnetic iron cores offered great contrast in MRI images with r2 = 11.8 ± 0.8 mM−1 s−1 (at 1 T), while Au satellites showed X-ray attenuation in CT. The intravenous injection of nanoparticles enabled clear tumor border visualization in mice. Plasmonic peak in the Fe-Au hybrids had a tail in the near-infrared region (NIR), allowing them to cause hyperthermia under 808 nm laser exposure. Under NIR irradiation Fe-Au particles provided 24.1 °C/W heating and an IC50 value below 32 µg/mL for three different cancer cell lines. Taken together, these results show that laser synthesized Fe-Au core-satellite nanoparticles are excellent theranostic agents with multimodal imaging and photothermal capabilities.

The combination of magnetic and plasmonic properties at the nanoscale promises the development of novel synergetic image-guided therapy strategies for the treatment of cancer and other diseases, but the fabrication of non-contaminated magneto-plasmonic nanocomposites suitable for biological applications is difficult within traditional chemical methods. Here, we describe a methodology based on laser ablation from Fe target in the presence of preliminarily ablated water-dispersed Au nanoparticles (NPs) to synthesize ultrapure bare (ligand-free) core-satellite nanostructures, consisting of large (several tens of nm) Fe-based core decorated by small (mean size 7.5 nm) Au NPs. The presence of the Fe-based core conditions a relatively strong magnetic response of the nanostructures (magnetization of >12.6 emu/g), while the Au NPs-based satellite shell provides a broad extinction peak centered at 550 nm with a long tale in the near-infrared to overlap with the region of relative tissue transparency (650–950 nm). We also discuss possible mechanisms responsible for the formation of the magnetic-plasmonic nanocomposites. We finally demonstrate a protocol to enhance colloidal stability of the core-satellites in biological environment by their coating with different polymers. Exempt of toxic impurities and combining strong magnetic and plasmonic responses, the formed core-satellite nanocomposites can be used in biomedical applications, including photo- and magneto-induced therapies, magnetic resonance imaging or photoacoustic imaging.

Herein, we report the fabrication and characterization of novel polycaprolactone (PCL)-based nanofibers functionalized with bare (ligand-free) titanium nitride (TiN) nanoparticles (NPs) for tissue engineering applications. Nanofibers were prepared by a newly developed protocol based on the electrospinning of PCL solutions together with TiN NPs synthesized by femtosecond laser ablation in acetone. The generated hybrid nanofibers were characterised using spectroscopy, microscopy, and thermal analysis techniques. As shown by scanning electron microscopy measurements, the fabricated electrospun nanofibers had uniform morphology, while their diameter varied between 0.403 ± 0.230 µm and 1.1 ± 0.15 µm by optimising electrospinning solutions and parameters. Thermal analysis measurements demonstrated that the inclusion of TiN NPs in nanofibers led to slight variation in mass degradation initiation and phase change behaviour (Tm). In vitro viability tests using the incubation of 3T3 fibroblast cells in a nanofiber-based matrix did not reveal any adverse effects, confirming the biocompatibility of hybrid nanofiber structures. The generated hybrid nanofibers functionalized with plasmonic TiN NPs are promising for the development of smart scaffold for tissue engineering platforms and open up new avenues for theranostic applications.

Owing to strong plasmonic absorption and excellent biocompatibility, gold nanostructures are among best candidates for photoacoustic bioimaging and photothermal therapy, but such applications require ultrapure Au-based nanoformulations of complex geometry (core-shells, nanorods) in order to shift the absorption band toward the region of relative tissue transparency (650–1000 nm). Here, we present a methodology for the fabrication of Si@Au core-satellite nanostructures, comprising of a Si core covered with small Au nanoparticles (NP), based on laser ablative synthesis of Si and Au NPs in water/ethanol solutions, followed by a chemical modification of the Si NPs by 3-aminopropyltrimethoxysilane (APTMS) and their subsequent decoration by the Au NPs. We show that the formed core-satellites have a red-shifted plasmonic absorption feature compared to that of pure Au NPs (520 nm), with the position of the peak depending on APTMS amount, water−ethanol solvent percentage and Si−Au volume ratio. As an example, even relatively small 40-nm core-satellites (34 nm Si core + 4 nm Au shell) provided a much red shifted peak centered around 610 nm and having a large tail over 700 nm. The generation of the plasmonic peak is confirmed by modeling of Si@Au core-shells of relevant parameters via Mie theory. Being relatively small and exempt of any toxic impurity due to ultraclean laser synthesis, the Si@Au core-satellites promise a major advancement of imaging and phototherapy modalities based on plasmonic properties of nanomaterials.

Elemental bismuth (Bi) nanoparticles (NPs), with the high atomic density of the Bi nuclei, could serve as efficient targeted agents for cancer treatment, with applications such as contrast agents for computed tomography (CT) imaging, sensitizers for image-guided X-ray radiotherapy, and photothermal therapy. However, the synthesis of elemental Bi NPs suitable for biological applications is difficult using conventional chemical routes. Here, we explore the fabrication of ultrapure Bi-based nanomaterials by femtosecond laser ablation from a solid Bi target in ambient liquids and characterize them by a variety of techniques, including TEM, SEM, XRD, FTIR, Raman, and optical spectroscopy. We found that laser-ablative synthesis using an elemental Bi solid target leads to the formation of spherical Bi NPs having the mean size of 20–50 nm and a low size-dispersion. The NPs prepared in water experience a fast (within a few minutes) conversion into 400–500 nm flake-like nanosheets, composed of bismuth subcarbonates, (BiO)2CO3 and (BiO)4CO3(OH)2, while the NPs prepared in acetone demonstrate high elemental stability. We introduce a procedure to obtain a stable aqueous solution of elemental Bi NPs suitable for biological applications, based on the coating of Bi NPs prepared in acetone with Pluronic® F68 and their subsequent transfer to water. We also show that the laser-synthesized elemental Bi NPs, due to their vanishing band gap, exhibit remarkable absorption in the infrared range, which can be used for the activation of photothermal therapy in the near IR-to-IR window with maximum optical transparency in biological media. Exempt of any toxic synthetic by-products, laser-ablated elemental Bi NPs present a novel appealing nanoplatform for combination image-guided photoradiotherapies.

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.

Gold nanoparticles (NPs) have a wide range of applications in various fields. Here, we present high-order nonlinear optical studies of the plasmas produced from ablation of Au bulk targets and Au NP films deposited on paper and glass substrates. Experimentally, we analyze high-order harmonic generation (HHG) from gold NPs-containing plasmas. The HHG is produced by 35-fs pulses at 800 and 400 nm, while the plasmas are produced by femtosecond (35 fs, 800 nm), picosecond (200 ps, 800 nm), and nanosecond (5 ns, 1064 nm) pulses, respectively. High-order harmonics produced from ablated Au NPs on paper were 40 times stronger than the HHG from that ablated from the Au bulk targets. Through molecular dynamic simulations, we investigate the formation of gold NPs during laser ablation of a metal surface under different conditions.

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 of 152Sm-enriched samarium oxide nanoparticles (NPs), which can capture neutrons to become 153Sm beta-emitters for nuclear therapy. We show that direct ablation of a 152Sm-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.

We present a framework based on the atomistic continuum model, combining the Molecular Dynamics (MD) and Two Temperature Model (TTM) approaches, to characterize the growth of metal nanoparticles (NPs) under ultrashort laser ablation from a solid target in water ambient. The model is capable of addressing the kinetics of fast non-equilibrium laser-induced phase transition processes at atomic resolution, while in continuum it accounts for the effect of free carriers, playing a determinant role during short laser pulse interaction processes with metals. The results of our simulations clarify possible mechanisms, which can be responsible for the observed experimental data, including the presence of two populations of NPs, having a small (5−15 nm) and larger (tens of nm) mean size. The formed NPs are of importance for a variety of applications in energy, catalysis and healthcare.

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.

We report a size-controllable synthesis of stable aqueous solutions of ultrapure low-size-dispersed Au nanoparticles by methods of femtosecond laser fragmentation from preliminary formed colloids. Such approach makes possible the tuning of mean nanoparticle size between a few nm and several tens of nm under the size dispersion lower than 70% by varying the fluence of pumping radiation during the fragmentation procedure. The efficient size control is explained by 3D geometry of laser fragmentation by femtosecond laser-induced white light super-continuum and plasma-related phenomena. Despite the absence of any protective ligands, the nanoparticle solutions demonstrate exceptional stability due to electric repulsion effect associated with strong negative charging of formed nanoparticles. Stable aqueous solutions of bare gold nanoparticles present a unique object with a variety of potential applications in catalysis, surface-enhanced Raman spectroscopy, photovoltaics, biosensing and biomedicine. [ABSTRACT FROM AUTHOR]

We report the synthesis of novel inorganic contamination-free photosensitizers based on colloidal silicon nanoparticles prepared by laser ablation in pure deionized water. We show that such nanoparticles are capable of generating singlet oxygen (1O2)under laser irradiation with a yield estimated at 10 of that of photofrin, which makes them a potential candidate for therapeutics, antiseptics, or disinfectants. We also discuss a model of 1O2generation and the possibility for optimizing its release. Potential advantages of such novel inorganic photosensitizers include stable and nonphotobleaching 1O2release, easy removal, and low dark toxicity. [ABSTRACT FROM AUTHOR]