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Florian Correard,1,2 Ksenia Maximova,3 Marie-Anne Estève,1,2 Claude Villard,1 Myriam Roy,4 Ahmed Al-Kattan,3 Marc Sentis,3 Marc Gingras,4 Andrei V Kabashin,3 Diane Braguer1,2 1Aix Marseille Université, INSERM, CR02 UMR_S911, Marseille, France; 2APHM, Hôpital Timone, Marseille, France; 3Aix Marseille Université, CNRS, LP3 UMR 7341, Marseille, France; 4Aix Marseille Université, CNRS, CINAM, UMR 7325 Marseille, France Abstract: Due to excellent biocompatibility, chemical stability, and promising optical properties, gold nanoparticles (Au-NPs) are the focus of research and applications in nanomedicine. Au-NPs prepared by laser ablation in aqueous biocompatible solutions present an essentially novel object that is unique in avoiding any residual toxic contaminant. This paper is conceived as the next step in development of laser-ablated Au-NPs for future in vivo applications. The aim of the study was to assess the safety, uptake, and biological behavior of laser-synthesized Au-NPs prepared in water or polymer solutions in human cell lines. Our results showed that laser ablation allows the obtaining of stable and monodisperse Au-NPs in water, polyethylene glycol, and dextran solutions. The three types of Au-NPs were internalized in human cell lines, as shown by transmission electron microscopy. Biocompatibility and safety of Au-NPs were demonstrated by analyzing cell survival and cell morphology. Furthermore, incubation of the three Au-NPs in serum-containing culture medium modified their physicochemical characteristics, such as the size and the charge. The composition of the protein corona adsorbed on Au-NPs was investigated by mass spectrometry. Regarding composition of complement C3 proteins and apolipoproteins, Au-NPs prepared in dextran solution appeared as a promising drug carrier. Altogether, our results revealed the safety of laser-ablated Au-NPs in human cell lines and support their use for theranostic applications. Keywords: protein corona, nanocarrier, cytotoxicity, green chemistry, neuroblastoma, glioblastoma

Abstract An overview of pulsed laser-assisted methods for nanofabrication, which are currently developed in our Institute (LP3), is presented. The methods compass a variety of possibilities for material nanostructuring offered by laser–matter interactions and imply either the nanostructuring of the laser-illuminated surface itself, as in cases of direct laser ablation or laser plasma-assisted treatment of semiconductors to form light-absorbing and light-emitting nano-architectures, as well as periodic nanoarrays, or laser-assisted production of nanoclusters and their controlled growth in gaseous or liquid medium to form nanostructured films or colloidal nanoparticles. Nanomaterials synthesized by laser-assisted methods have a variety of unique properties, not reproducible by any other route, and are of importance for photovoltaics, optoelectronics, biological sensing, imaging and therapeutics.

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.

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., (© 2024. Pleiades Publishing, Ltd.)

Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold-NP-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic NPs based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable to or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. Since the main cost of Au NPs in commercial testing kits is the colloidal synthesis, our development with the Cu@Au and the laser-ablation-fabricated TiN NPs is exciting, offering potentially inexpensive plasmonic nanomaterials for various bioapplications. Moreover, our machine learning study showed that biodetection with TiN is more accurate than that with Au.

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., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 μg/ml; the LC 50 value was 57 μg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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 10 B 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.

Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH 2 MOFs and conjugated them with clinically utilized radionuclide 188 Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq mg -1 . Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was (20.9 ± 1.3) h, and nanoparticles enabled it to passively accumulate and retain in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH 2 for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine., (© 2023 IOP Publishing Ltd.)

Due to the absence of labels and fast analyses, optical biosensors promise major advances in biomedical diagnostics, security, environmental, and food safety applications. However, the sensitivity of the most advanced plasmonic biosensor implementations has a fundamental limitation caused by losses in the system and/or geometry of biochips. Here, we report a "scissor effect" in topologically dark metamaterials which is capable of providing ultrahigh-amplitude sensitivity to biosensing events, thus solving the bottleneck sensitivity limitation problem. We explain how the "scissor effect" can be realized via the proper design of topologically dark metamaterials and describe strategies for their fabrication. To validate the applicability of this effect in biosensing, we demonstrate the detection of folic acid (vitamin important for human health) in a wide 3-log linear dynamic range with a limit of detection of 0.22 nM, which is orders of magnitude better than those previously reported for all optical counterparts. Our work provides possibilities for designing and realizing plasmonic, semiconductor, and dielectric metamaterials with ultrasensitivity to binding events.

Label-free optical biosensing holds great promise for a variety of applications in biomedical diagnostics, environmental and food safety, and security. It is already used as a key tool in the investigation of biomolecular binding events and reaction constants in real time and offers further potential additional functionalities and low-cost designs. However, the sensitivity of this technology does not match the routinely used but expensive and slow labelling methods. Therefore, label-free optical biosensing remains predominantly a research tool. Here we discuss how one can go beyond the limits of detection provided by standard optical biosensing platforms and achieve a sensitivity of label-free biosensing that is superior to labelling methods. To this end we review newly emerging optical implementations that overcome current sensitivity barriers by employing novel structural architectures, artificial materials (metamaterials and hetero-metastructures) and using phase of light as a sensing parameter. Furthermore, we elucidate the mechanism of plasmonic phase biosensing and review hyper-sensitive transducers, which can achieve detection limits at the single molecule level (less than 1 fg mm -2 ) and make it possible to detect analytes at several orders of magnitude lower concentrations than so far reported in literature. We finally discuss newly emerging layouts based on dielectric nanomaterials, bound states in continuum, and exceptional points.

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.

Recent developments in the area of resonant dielectric nanostructures have created attractive opportunities for concentrating and manipulating light at the nanoscale and the establishment of the new exciting field of all-dielectric nanophotonics. Transition metal dichalcogenides (TMDCs) with nanopatterned surfaces are especially promising for these tasks. Still, the fabrication of these structures requires sophisticated lithographic processes, drastically complicating application prospects. To bridge this gap and broaden the application scope of TMDC nanomaterials, we report here femtosecond laser-ablative fabrication of water-dispersed spherical TMDC (MoS 2 and WS 2 ) nanoparticles (NPs) of variable size (5 to 250 nm). Such NPs demonstrate exciting optical and electronic properties inherited from TMDC crystals, due to preserved crystalline structure, which offers a unique combination of pronounced excitonic response and high refractive index value, making possible a strong concentration of electromagnetic field in the NPs. Furthermore, such NPs offer additional tunability due to hybridization between the Mie and excitonic resonances. Such properties bring to life a number of nontrivial effects, including enhanced photoabsorption and photothermal conversion. As an illustration, we demonstrate that the NPs exhibit a very strong photothermal response, much exceeding that of conventional dielectric nanoresonators based on Si. Being in a mobile colloidal state and exhibiting superior optical properties compared to other dielectric resonant structures, the synthesized TMDC NPs offer opportunities for the development of next-generation nanophotonic and nanotheranostic platforms, including photothermal therapy and multimodal bioimaging.

Bismuth-based compounds are considered to be the best candidates for computed tomography (CT) imaging of gastrointestinal (GI) tract due to high X-ray absorption. Here, we report the introduction of polymer-coated bismuth oxychloride (BiOCl) nanosheets for highly efficient CT imaging in healthy mice and animal with colitis. We demonstrate simple, low cost and fast aqueous synthesis protocol which provides gram-quantity yield of chemically stable BiOCl nanosheets. The developed contrast gives 2.55-fold better CT enhancement compared to conventional contrast with negligible in vivo toxicity. As a major finding we report a regioselective CT imaging of GI tract by using nanoparticles coated with differentially charged polymers. Coating of nanoparticles with a positively charged polymer leads to their fast accumulation in small intestine, while the coating with negatively charged polymers stimulates prolonged stomach retention. We propose that this effect may be explained by a pH-controlled aggregation of nanoparticles in stomach. This feature may become the basis for advancement in clinical diagnosis of entire GI tract., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Due to particular physico-chemical characteristics and prominent optical properties, nanostructured germanium (Ge) appears as a promising material for biomedical applications, but its use in biological systems has been limited so far due to the difficulty of preparation of Ge nanostructures in a pure, uncontaminated state. Here, we explored the fabrication of Ge nanoparticles (NPs) using methods of pulsed laser ablation in ambient gas (He or He-N 2 mixtures) maintained at low residual pressures (1-5 Torr). We show that the ablated material can be deposited on a substrate (silicon wafer in our case) to form a nanostructured thin film, which can then be ground in ethanol by ultrasound to form a stable suspension of Ge NPs. It was found that these formed NPs have a wide size dispersion, with sizes between a few nm and hundreds of nm, while a subsequent centrifugation step renders possible the selection of one or another NP size fraction. Structural characterization of NPs showed that they are composed of aggregations of Ge crystals, covered by an oxide shell. Solutions of the prepared NPs exhibited largely dominating photoluminescence (PL) around 450 nm, attributed to defects in the germanium oxide shell, while a separated fraction of relatively small (5-10 nm) NPs exhibited a red-shifted PL band around 725 nm under 633 nm excitation, which could be attributed to quantum confinement effects. It was also found that the formed NPs exhibit high absorption in the visible and near-IR spectral ranges and can be strongly heated under photoexcitation in the region of relative tissue transparency, which opens access to phototherapy functionality. Combining imaging and therapy functionalities in the biological transparency window, laser-synthesized Ge NPs present a novel promising object for cancer theranostics.

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 (H 3 BO 3 ) 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., (© 2022. The Author(s).)

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 H 2 O 2 , 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 TiO 2 , 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 H 2 O 2 ), 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 r 2 = 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 IC 50 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.

Nuclear medicine is expected to make major advances in cancer diagnosis and therapy; tumor-targeted radiopharmaceuticals preferentially eradicate tumors while causing minimal damage to healthy tissues. The current scope of nuclear medicine can be significantly expanded by integration with nanomedicine, which utilizes nanoparticles for cancer diagnosis and therapy by capitalizing on the increased surface area-to-volume ratio, the passive/active targeting ability and high loading capacity, the greater interaction cross section with biological tissues, the rich surface properties of nanomaterials, the facile decoration of nanomaterials with a plethora of functionalities, and the potential for multiplexing several functionalities within one construct. This review provides a comprehensive discussion of nuclear nanomedicine using tumor-targeted nanoparticles for cancer radiation therapy with either pre-embedded radionuclides or nonradioactive materials which can be extrinsically triggered using various external nuclear particle sources to produce in situ radioactivity. In addition, it describes the prospect of combining nuclear nanomedicine with other modalities to enable synergistically enhanced combination therapies. The review also discusses advances in the fabrication of radionuclides as well as describes laser ablation technologies for producing nanoradiopharmaceuticals, which combine the ease of production with exceptional purity and rapid biodegradability, along with additional imaging or therapeutic functionalities. From a practical standpoint, these attributes of nanoradiopharmaceuticals may provide distinct advantages in diagnostic/therapeutic sensitivity and specificity, imaging resolution, and scalability of turnkey platforms. Coupling image-guided targeted radiation therapy with the possibility of in situ activation of nanomaterials as well as combining with other therapeutic modalities using a multifunctional nanoplatform could herald an era of exciting technological and therapeutic advances to radically transform the landscape of nuclear medicine. The review concludes with a discussion of current challenges and presents the authors' views on future opportunities to stimulate further research in this rewarding field of high societal impact.

Photodynamic therapy (PDT) is one of the most appealing photonic modalities for cancer treatment based on anticancer activity of light-induced photosensitizer-mediated reactive oxygen species (ROS), but a limited depth of light penetration into tissues does not make possible the treatment of deep-seated neoplasms and thus complicates its widespread clinical adoption. Here, we introduce the concept of genetically encoded bioluminescence resonance energy transfer (BRET)-activated PDT, which combines an internal light source and a photosensitizer (PS) in a single-genetic construct, which can be delivered to tumors seated at virtually unlimited depth and then triggered by the injection of a substrate to initiate their treatment. To illustrate the concept, we engineered genetic NanoLuc-miniSOG BRET pair, combining NanoLuc luciferase flashlight and phototoxic flavoprotein miniSOG, which generates ROS under luciferase-substrate injection. We prove the concept feasibility in mice bearing NanoLuc-miniSOG expressing tumor, followed by its elimination under the luciferase-substrate administration. Then, we demonstrate a targeted delivery of NanoLuc-miniSOG gene, via tumor-specific lentiviral particles, into a tumor, followed by its successful elimination, with tumor-growth inhibition (TGI) coefficient exceeding 67%, which confirms a great therapeutic potential of the proposed concept. In conclusion, this study provides proof-of-concept for deep-tissue "photodynamic" therapy without external light source that can be considered as an alternative for traditional PDT., (© 2022. The Author(s).)

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.

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.

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 (T m ). 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.

Having plasmonic absorption within the biological transparency window, titanium nitride (TiN) nanoparticles (NPs) can potentially outperform gold counterparts in phototheranostic applications, but characteristics of available TiN NPs are still far from required parameters. Recently emerged laser-ablative synthesis opens up opportunities to match these parameters as it makes possible the production of ultrapure low size-dispersed spherical TiN NPs, capable of generating a strong phototherapy effect under 750-800 nm excitation. This study presents the first assessment of toxicity, biodistribution and pharmacokinetics of laser-synthesized TiN NPs. Tests in vitro using 8 cell lines from different tissues evidenced safety of both as-synthesized and PEG-coated NPs (TiN-PEG NPs). After systemic administration in mice, they mainly accumulated in liver and spleen, but did not cause any sign of toxicity or organ damage up to concentration of 6 mg kg -1 , which was confirmed by the invariability of blood biochemical parameters, weight and hemotoxicity examination. The NPs demonstrated efficient passive accumulation in EMT6/P mammary tumor, while concentration of TiN-PEG NPs was 2.2-fold higher due to "stealth" effect yielding 7-times longer circulation in blood. The obtained results evidence high safety of laser-synthesized TiN NPs for biological systems, which promises a major advancement of phototheranostic modalities on their basis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A nonlinear photoacoustic (PA) response from solutions of 40 nm plasmonic titanium nitride nanoparticles (NPs) synthesized by laser ablation in a liquid environment (acetone) is reported. Using a photoacoustic Z-scan with 5 ns pumping pulses, values of effective nonlinear absorption (NLA) coefficients β PA,eff were measured and found to be 3.27±0.17 × 10 -8 , 6.41±0.32 × 10 -8 , and 3.22±0.16 × 10 -8 for 600, 700, and 800 nm pumping wavelengths, respectively. To take into account the influence of nonlinear scattering, absorption-dependent PA measurements were carried out together with the optical Z-scan, and the obtained data were compared. The origin of the effective absorptive nonlinearity is discussed based on combined NLA in NPs, nonlinear scattering, and bubble generation triggered by NP-mediated light absorption. Potential applications include biomedical diagnostics and therapy.

When combined with immunotherapy, image-guided targeted delivery of chemotherapeutic agents is a promising direction for combination cancer theranostics, but this approach has so far produced only limited success due to a lack of molecular targets on the cell surface and low therapeutic index of conventional chemotherapy drugs. Here, we demonstrate a synergistic strategy of combination immuno/chemotherapy in conditions of dual regioselective targeting, implying vectoring of two distinct binding sites of a single oncomarker (here, HER2) with theranostic compounds having a different mechanism of action. We use: (i) PLGA nanoformulation, loaded with an imaging diagnostic fluorescent dye (Nile Red) and a chemotherapeutic drug (doxorubicin), and functionalized with affibody Z HER2:342 (8 kDa); (ii) bifunctional genetically engineered DARP-LoPE (42 kDa) immunotoxin comprising of a low-immunogenic modification of therapeutic Pseudomonas exotoxin A (LoPE) and a scaffold targeting protein, DARPin9.29 (14 kDa). According to the proposed strategy, the first chemotherapeutic nanoagent is targeted by the affibody to subdomain III and IV of HER2 with 60-fold specificity compared with nontargeted particles, while the second immunotoxin is effectively targeted by DARPin molecule to subdomain I of HER2. We demonstrate that this dual targeting strategy can enhance anticancer therapy of HER2-positive cells with a very strong synergy, which made possible 1000-fold decrease of effective drug concentration in vitro and a significant enhancement of HER2 cancer therapy compared to monotherapy in vivo . Moreover, this therapeutic combination prevented the appearance of secondary tumor nodes. Thus, the suggested synergistic strategy utilizing dual targeting of the same oncomarker could give rise to efficient methods for aggressive tumors treatment.

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) 2 CO 3 and (BiO) 4 CO 3 (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.

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.

Using methods of pulsed laser ablation from a silicon target in helium (He)-nitrogen (N 2 ) 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/N 2 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-SiO x ) coating, respectively, while the addition of N 2 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-SiN x O y ) coating of Si nanocrystals. PL transients of Si nanocrystals with SiO x and a-SiN x O y 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., Competing Interests: The authors declare no conflict of interest.

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

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

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.

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.

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

Exhibiting a red-shifted absorption/scattering feature compared to conventional plasmonic metals, titanium nitride nanoparticles (TiN NPs) look as very promising candidates for biomedical applications, but these applications are still underexplored despite the presence of extensive data for conventional plasmonic counterparts. Here, we report the fabrication of ultrapure, size-tunable TiN NPs by methods of femtosecond laser ablation in liquids and their biological testing. We show that TiN NPs demonstrate strong and broad plasmonic peak around 640-700 nm with a significant tail over 800 nm even for small NPs sizes (<7 nm). In vitro tests of laser-synthesized TiN NPs on cellular models evidence their low cytotoxicity and excellent cell uptake. We finally demonstrate a strong photothermal therapy effect on U87-MG cancer cell cultures using TiN NPs as sensitizers of local hyperthermia under near-infrared laser excitation. Based on absorption band in the region of relative tissue transparency and acceptable biocompatibility, laser-synthesized TiN NPs promise the advancement of biomedical modalities employing plasmonic effects, including absorption/scattering contrast imaging, photothermal therapy, photoacoustic imaging and SERS.

The ability of noble metal-based nanoparticles (NPs) (Au, Ag) to drastically enhance Raman scattering from molecules placed near metal surface, termed as surface-enhanced Raman scattering (SERS), is widely used for identification of trace amounts of biological materials in biomedical, food safety and security applications. However, conventional NPs synthesized by colloidal chemistry are typically contaminated by nonbiocompatible by-products (surfactants, anions), which can have negative impacts on many live objects under examination (cells, bacteria) and thus decrease the precision of bioidentification. In this article, we explore novel ultrapure laser-synthesized Au-based nanomaterials, including Au NPs and AuSi hybrid nanostructures, as mobile SERS probes in tasks of bacteria detection. We show that these Au-based nanomaterials can efficiently enhance Raman signals from model R6G molecules, while the enhancement factor depends on the content of Au in NP composition. Profiting from the observed enhancement and purity of laser-synthesized nanomaterials, we demonstrate successful identification of 2 types of bacteria (Listeria innocua and Escherichia coli). The obtained results promise less disturbing studies of biological systems based on good biocompatibility of contamination-free laser-synthesized nanomaterials., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

When metal nanoparticles are arranged in an ordered array, they may scatter light to produce diffracted waves. If one of the diffracted waves then propagates in the plane of the array, it may couple the localized plasmon resonances associated with individual nanoparticles together, leading to an exciting phenomenon, the drastic narrowing of plasmon resonances, down to 1-2 nm in spectral width. This presents a dramatic improvement compared to a typical single particle resonance line width of >80 nm. The very high quality factors of these diffractively coupled plasmon resonances, often referred to as plasmonic surface lattice resonances, and related effects have made this topic a very active and exciting field for fundamental research, and increasingly, these resonances have been investigated for their potential in the development of practical devices for communications, optoelectronics, photovoltaics, data storage, biosensing, and other applications. In the present review article, we describe the basic physical principles and properties of plasmonic surface lattice resonances: the width and quality of the resonances, singularities of the light phase, electric field enhancement, etc. We pay special attention to the conditions of their excitation in different experimental architectures by considering the following: in-plane and out-of-plane polarizations of the incident light, symmetric and asymmetric optical (refractive index) environments, the presence of substrate conductivity, and the presence of an active or magnetic medium. Finally, we review recent progress in applications of plasmonic surface lattice resonances in various fields.

Driven by surface cleanness and unique physical, optical and chemical properties, bare (ligand-free) laser-synthesized nanoparticles (NPs) are now in the focus of interest as promising materials for the development of advanced biomedical platforms related to biosensing, bioimaging and therapeutic drug delivery. We recently achieved significant progress in the synthesis of bare gold (Au) and silicon (Si) NPs and their testing in biomedical tasks, including cancer imaging and therapy, biofuel cells, etc. We also showed that these nanomaterials can be excellent candidates for tissue engineering applications. This review is aimed at the description of our recent progress in laser synthesis of bare Si and Au NPs and their testing as functional modules (additives) in innovative scaffold platforms intended for tissue engineering tasks.

When excited over a periodic metamaterial lattice of gold nanoparticles (~ 100nm), localized plasmon resonances (LPR) can be coupled by a diffraction wave propagating along the array plane, which leads to a drastic narrowing of plasmon resonance lineshapes (down to a few nm full-width-at-half-maximum) and the generation of singularities of phase of reflected light. These phenomena look very promising for the improvement of performance of plasmonic biosensors, but conditions of implementation of such diffractively coupled plasmonic resonances, also referred to as plasmonic surface lattice resonances (PSLR), are not always compatible with biosensing arrangement implying the placement of the nanoparticles between a glass substrate and a sample medium (air, water). Here, we consider conditions of excitation and properties of PSLR over arrays of glass substrate-supported single and double Au nanoparticles (~ 100-200nm), arranged in a periodic metamaterial lattice, in direct and Attenuated Total Reflection (ATR) geometries, and assess their sensitivities to variations of refractive index (RI) of the adjacent sample dielectric medium. First, we identify medium (PSLR air , PSLR wat for air and water, respectively) and substrate (PSLR sub ) modes corresponding to the coupling of individual plasmon oscillations at medium- and substrate-related diffraction cut-off edges. We show that spectral sensitivity of medium modes to RI variations is determined by the lattice periodicity in both direct and ATR geometries (~ 320nm per RIU change in our case), while substrate mode demonstrates much lower sensitivity. We also show that phase sensitivity of PSLR can exceed 10 5 degrees of phase shift per RIU change and thus outperform the relevant parameter for all other plasmonic sensor counterparts. We finally demonstrate the applicability of surface lattice resonances in plasmonic metamaterial arrays to biosensing using standard streptavidin-biotin affinity model. Combining advantages of nanoscale architectures, including drastic concentration of electric field, possibility of manipulation at the nanoscale etc, and high phase and spectral sensitivities, PSLRs promise the advancement of current state-of-the-art plasmonic biosensing technology toward single molecule label-free detection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Continuous wave (CW) radiation from a Yb-fiber laser (central wavelength 1064 nm, power 1-200 W) was used to initiate ablation of a gold target in deionized water and to synthesize bare (unprotected) gold nanoparticles. We show that the formed nanoparticles present a single low-size-dispersed population with a mean size of the order of 10 nm, which contrasts with previously reported data on dual populations of nanoparticles formed during pulsed laser ablation in liquids. The lack of a second population of nanoparticles is explained by the absence of cavitation-related mechanism of material ablation, which typically takes place under pulsed laser action on a solid target in liquid ambience, and this supposition is confirmed by plume visualization tests. We also observe a gradual growth of mean nanoparticle size from 8-10 nm to 20-25 nm under the increase of laser power for 532 nm pumping wavelength, whereas for 1064 nm pumping wavelength the mean size 8-10 nm is independent of radiation power. The growth of the nanoparticles observed for 532 nm wavelength is attributed to the enhanced target melting and splashing followed by additional heating due to an efficient excitation of plasmons over gold nanoparticles. Bare, low-size-dispersed gold nanoparticles are of importance for a variety of applications, including biomedicine, catalysis, and photovoltaics. The use of CW radiation for nanomaterial production promises to improve the cost efficiency of this technology., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We employ a method of femtosecond laser fragmentation of preliminarily prepared water-dispersed microcolloids to fabricate aqueous solutions of ultrapure bare Si-based nanoparticles (Si-NPs) and assess their potential for biomedical applications. The nanoparticles appear spherical in shape, with low size dispersion and a controllable mean size, from a few nm to several tens of nm, while a negative surface charge (-35 mV ± 0.10 according to z-potential data) provides good electrostatic stabilization of colloidal Si-NP solutions. Structural analysis shows that the Si-NPs are composed of Si nanocrystals with inclusions of silicon oxide species, covered by a SiO x (1 < x < 2) shell, while the total oxide content depends on whether the fragmentation is performed in normal oxygen-saturated water (oxygen-rich conditions) or in water deoxygenated by pumping with noble gases (Ag or He) before and during the experiment (oxygen-free conditions). Our dissolution tests show the excellent water-solubility of all the NPs, while more oxidized NPs demonstrate much faster dissolution kinetics, which is explained by oxidation-induced defects in the core of the Si-NPs. Finally, by examining the interaction of the NPs with human cells after 72 h of incubation at different concentrations, we report the absence of any adverse effects of the NPs up to high concentrations (50 μg mL -1 ) and a good internalization of NPs via a classical endocytosis mechanism. Possessing far superior purity compared to their chemically synthesized counterparts and enabling a variety of imaging and therapeutic functionalities, the laser-synthesized Si-NPs are promising for safe and efficient applications in nanomedicine.

We explore the excitation of plasmons in 3D plasmon crystal metamaterials and report the observation of a delocalized plasmon mode, which provides extremely high spectral sensitivity (>2600 nm per refractive index unit (RIU) change), outperforming all plasmonic counterparts excited in 2D nanoscale geometries, as well as a prominent phase-sensitive response (>3*10(4) deg. of phase per RIU). Combined with a large surface for bioimmobilization provided by the 3D matrix, the proposed sensor architecture promises a new important landmark in the advancement of plasmonic biosensing technology.

Si/SiOx nanoparticles (NPs) produced by laser ablation in deionized water or aqueous biocompatible solutions present a novel extremely promising object for biomedical applications, but the interaction of these NPs with biological systems has not yet been systematically examined. Here, we present the first comprehensive study of biodistribution, biodegradability and toxicity of laser-synthesized Si-SiOx nanoparticles using a small animal model. Despite a relatively high dose of Si-NPs (20 mg/kg) administered intravenously in mice, all controlled parameters (serum, enzymatic, histological etc.) were found to be within safe limits 3 h, 24 h, 48 h and 7 days after the administration. We also determined that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine without any toxicity effects. Finally, we found that intracellular accumulation of Si-NPs does not induce any oxidative stress damage. Our results evidence a huge potential in using these safe and biodegradable NPs in biomedical applications, in particular as vectors, contrast agents and sensitizers in cancer therapy and diagnostics (theranostics).

Crystalline silicon (Si) nanoparticles present an extremely promising object for bioimaging based on photoluminescence (PL) in the visible and near-infrared spectral regions, but their efficient PL emission in aqueous suspension is typically observed after wet chemistry procedures leading to residual toxicity issues. Here, we introduce ultrapure laser-synthesized Si-based quantum dots (QDs), which are water-dispersible and exhibit bright exciton PL in the window of relative tissue transparency near 800 nm. Based on the laser ablation of crystalline Si targets in gaseous helium, followed by ultrasound-assisted dispersion of the deposited films in physiological saline, the proposed method avoids any toxic by-products during the synthesis. We demonstrate efficient contrast of the Si QDs in living cells by following the exciton PL. We also show that the prepared QDs do not provoke any cytoxicity effects while penetrating into the cells and efficiently accumulating near the cell membrane and in the cytoplasm. Combined with the possibility of enabling parallel therapeutic channels, ultrapure laser-synthesized Si nanostructures present unique object for cancer theranostic applications.