Reagentless Glucose Biosensor Based on Combination of Platinum Nanostructures and Polypyrrole Layer.

Two types of low-cost reagentless electrochemical glucose biosensors based on graphite rod (GR) electrodes were developed. The electrodes modified with electrochemically synthesized platinum nanostructures (PtNS), 1,10-phenanthroline-5,6-dione (PD), glucose oxidase (GOx) without and with a polypyrrole (Ppy) layer-(i) GR/PtNS/PD/GOx and (ii) GR/PtNS/PD/GOx/Ppy, respectively, were prepared and tested. Glucose biosensors based on GR/PtNS/PD/GOx and GR/PtNS/PD/GOx/Ppy electrodes were characterized by the sensitivity of 10.1 and 5.31 µA/(mM cm2), linear range (LR) up to 16.5 and 39.0 mM, limit of detection (LOD) of 0.198 and 0.561 mM, good reproducibility, and storage stability. The developed glucose biosensors based on GR/PtNS/PD/GOx/Ppy electrodes showed exceptional resistance to interfering compounds and proved to be highly efficient for the determination of glucose levels in blood serum.

Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy.

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.

Laser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy.

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

Calcein-Modified CeO2 for Intracellular ROS Detection: Mechanisms of Action and Cytotoxicity Analysis In Vitro.

Cerium oxide nanoparticles (CeO2 NPs) are metal-oxide-based nanozymes with unique reactive oxygen species (ROS) scavenging abilities. Here, we studied new CeO2 NPs modified with calcein (CeO2-calcein) as an intracellular ROS inactivation/visualization theranostic agent. The molecular mechanisms of the CeO2-calcein intracellular activity, allowing for the direct monitoring of ROS inactivation in living cells, were studied. CeO2-calcein was taken up by both normal (human mesenchymal stem cells, hMSc) and cancer (human osteosarcoma, MNNG/Hos cell line) cells, and was easily decomposed via endogenous or exogenous ROS, releasing brightly fluorescent calcein, which could be quantitatively detected using fluorescence microscopy. It was shown that the CeO2-calcein has selective cytotoxicity, inducing the death of human osteosarcoma cells and modulating the expression of key genes responsible for cell redox status as well as proliferative and migration activity. Such cerium-based theranostic agents can be used in various biomedical applications.

Hybrid Polyelectrolyte Capsules Loaded with Gadolinium-Doped Cerium Oxide Nanoparticles as a Biocompatible MRI Agent for Theranostic Applications.

Layer-by-layer (LbL) self-assembled polyelectrolyte capsules have demonstrated their unique advantages and capability in drug delivery applications. These ordered micro/nanostructures are also promising candidates as imaging contrast agents for diagnostic and theranostic applications. Magnetic resonance imaging (MRI), one of the most powerful clinical imaging modalities, is moving forward to the molecular imaging field and requires advanced imaging probes. This paper reports on a new design of MRI-visible LbL capsules, loaded with redox-active gadolinium-doped cerium oxide nanoparticles (CeGdO2-x NPs). CeGdO2-x NPs possess an ultrasmall size, high colloidal stability, and pronounced antioxidant properties. A comprehensive analysis of LbL capsules by TEM, SEM, LCSM, and EDX techniques was carried out. The research demonstrated a high level of biocompatibility and cellular uptake efficiency of CeGdO2-x-loaded capsules by cancer (human osteosarcoma and adenocarcinoma) cells and normal (human mesenchymal stem) cells. The LbL-based delivery platform can also be used for other imaging modalities and theranostic applications.

Boron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment.

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.

Laser-Ablative Synthesis of Silicon-Iron Composite Nanoparticles for Theranostic 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.

The Development and Evaluation of Reagentless Glucose Biosensors Using Dendritic Gold Nanostructures as a Promising Sensing Platform.

Reagentless electrochemical glucose biosensors were developed and investigated. A graphite rod (GR) electrode modified with electrochemically synthesized dendritic gold nanostructures (DGNs) and redox mediators (Med) such as ferrocenecarboxylic acid (FCA), 1,10-phenathroline-5,6-dione (PD), N,N,N',N'-tetramethylbenzidine (TMB) or tetrathiafulvalene (TTF) in combination with glucose oxidase (GOx) (GR/DGNs/FCA/GOx, GR/DGNs/PD/GOx, GR/DGNs/TMB/GOx, or GR/DGNs/TTF/GOx) were developed and electrochemically investigated. A biosensor based on threefold-layer-by-layer-deposited PD and GOx (GR/DGNs/(PD/GOx)3) was found to be the most suitable for the determination of glucose. To improve the performance of the developed biosensor, the surface of the GR/DGNs/(PD/GOx)3 electrode was modified with polypyrrole (Ppy) for 5 h. A glucose biosensor based on a GR/DGNs/(PD/GOx)3/Ppy(5 h) electrode was characterized using a wide linear dynamic range of up to 39.0 mmol L-1 of glucose, sensitivity of 3.03 µA mM-1 cm-2, limit of detection of 0.683 mmol L-1, and repeatability of 9.03% for a 29.4 mmol L-1 glucose concentration. The Ppy-based glucose biosensor was characterized by a good storage stability (τ1/2 = 9.0 days). Additionally, the performance of the developed biosensor in blood serum was investigated.

Stimulation of Chondrocyte and Bone Marrow Mesenchymal Stem Cell Chondrogenic Response by Polypyrrole and Polypyrrole/Gold Nanoparticles.

Bone marrow mesenchymal stem cells (BMMSCs) possess a strong ability to differentiate into the chondrogenic lineage, which is important for cartilage regeneration. External stimuli, such as electrical stimulation (ES), are frequently studied for chondrogenic differentiation of BMMSCs; however, the application of conductive polymers such as polypyrrole (Ppy), has never been used for stimulating BMMSCs chondrogenesis in vitro before. Thus, the aim of this study was to evaluate the chondrogenic potential of human BMMSCs after stimulation with Ppy nanoparticles (Ppy NPs) and compare them to cartilage-derived chondrocytes. In this study, we tested Ppy NPs without and with 13 nm gold NPs (Ppy/Au) for BMMSCs and chondrocyte proliferation, viability, and chondrogenic differentiation for 21 days, without the use of ES. The results demonstrated significantly higher amounts of cartilage oligomeric matrix protein (COMP) in BMMSCs stimulated with Ppy and Ppy/Au NPs, as compared to the control. The expression of chondrogenic genes (SOX9, ACAN, COL2A1) in BMMSCs and chondrocytes were upregulated by Ppy and Ppy/Au NPs, as compared to controls. Histological staining with safranin-O indicated higher extracellular matrix production in Ppy and Ppy/Au NPs stimulated samples, as compared to controls. In conclusion, Ppy and Ppy/Au NPs stimulate BMMSC chondrogenic differentiation; however, BMMSCs were more responsive to Ppy, while chondrocytes possessed a stronger chondrogenic response to Ppy/Au NPs.

Electrochemical Immunosensor for the Determination of Antibodies against Prostate-Specific Antigen Based on ZnO Nanostructures.

In this study, ZnO nanostructures with different types of morphologies and particle sizes were evaluated and applied for the development of an immunosensor. The first material was composed of spherical, polydisperse nanostructures with a particle size in the range of 10-160 nm. The second was made up of more compact rod-like spherical nanostructures with the diameter of these rods in the range of 50-400 nm, and approximately 98% of the particles were in the range of 20-70 nm. The last sample of ZnO was made up of rod-shaped particles with a diameter of 10-80 nm. These ZnO nanostructures were mixed with Nafion solution and drop-casted onto screen-printed carbon electrodes (SPCE), followed by a further immobilization of the prostate-specific antigen (PSA). The affinity interaction of PSA with monoclonal antibodies against PSA (anti-PSA) was evaluated using the differential pulse voltammetry technique. The limit of detection and limit of quantification of anti-PSA were determined as 1.35 nM and 4.08 nM for compact rod-shaped spherical ZnO nanostructures, and 2.36 nM and 7.15 nM for rod-shaped ZnO nanostructures, respectively.

Heavily Gd-Doped Non-Toxic Cerium Oxide Nanoparticles for MRI Labelling of Stem Cells.

Recently, human mesenchymal stem cells (hMSc) have attracted a great deal of attention as potential therapeutic agents in the treatment of socially significant diseases. Despite substantial advances in stem-cell therapy, the biological mechanisms of hMSc action after transplantation remain unclear. The use of magnetic resonance imaging (MRI) as a non-invasive method for tracking stem cells in the body is very important for analysing their distribution in tissues and organs, as well as for ensuring control of their lifetime after injection. Herein, detailed experimental data are reported on the biocompatibility towards hMSc of heavily gadolinium-doped cerium oxide nanoparticles (Ce0.8Gd0.2O2-x) synthesised using two synthetic protocols. The relaxivity of the nanoparticles was measured in a magnetic field range from 1 mT to 16.4 T. The relaxivity values (r1 = 11 ± 1.2 mM-1 s-1 and r1 = 7 ± 1.2 mM-1 s-1 in magnetic fields typical of 1.5 and 3 T MRI scanners, respectively) are considerably higher than those of the commercial Omniscan MRI contrast agent. The low toxicity of gadolinium-doped ceria nanoparticles to hMSc enables their use as an effective theranostic tool with improved MRI-contrasting properties.

Mitogen-like Cerium-Based Nanoparticles Protect Schmidtea mediterranea against Severe Doses of X-rays.

Novel radioprotectors are strongly demanded due to their numerous applications in radiobiology and biomedicine, e.g., for facilitating the remedy after cancer radiotherapy. Currently, cerium-containing nanomaterials are regarded as promising inorganic radioprotectors due to their unrivaled antioxidant activity based on their ability to mimic the action of natural redox enzymes like catalase and superoxide dismutase and to neutralize reactive oxygen species (ROS), which are by far the main damaging factors of ionizing radiation. The freshwater planarian flatworms are considered a promising system for testing new radioprotectors, due to the high regenerative potential of these species and an excessive amount of proliferating stem cells (neoblasts) in their bodies. Using planarian Schmidtea mediterranea, we tested CeO2 nanoparticles, well known for their antioxidant activity, along with much less studied CeF3 nanoparticles, for their radioprotective potential. In addition, both CeO2 and CeF3 nanoparticles improve planarian head blastema regeneration after ionizing irradiation by enhancing blastema growth, increasing the number of mitoses and neoblasts' survival, and modulating the expression of genes responsible for the proliferation and differentiation of neoblasts. The CeO2 nanoparticles' action stems directly from their redox activity as ROS scavengers, while the CeF3 nanoparticles' action is mediated by overexpression of "wound-induced genes" and neoblast- and stem cell-regulating genes.

BioSAXS at European Synchrotron Radiation Facility - Extremely Brilliant Source: BM29 with an upgraded source, detector, robot, sample environment, data collection and analysis software.

As part of its Extremely Brilliant Source (EBS) upgrade project, the ESRF's BM29 BioSAXS beamline was subject to a significant upgrade and refurbishment. In addition to the replacement of the beamline's original bending magnet source by a two-pole wiggler, leading to an increase in brilliance by a factor of 60, the sample environment of the beamline was almost completely refurbished: a vacuum-compatible Pilatus3 X 2M with a sensitive area of 253.7 mm × 288 mm and frame rates up to 250 Hz was installed, increasing the active area available and thus the q-scaling of scattering images taken; the sample changer was replaced with an upgraded version, allowing more space for customizable sample environments and the installation of two new sample exposure units; the software associated with the beamline was also renewed. In addition, the layout and functionality of the BSXCuBE3 (BioSAXS Customized Beamline Environment) data acquisition software was redesigned, providing an intuitive `user first' approach for inexperienced users, while at the same time maintaining more powerful options for experienced users and beamline staff. Additional features of BSXCuBE3 are queuing of samples; either consecutive sample changer and/or SEC-SAXS (size-exclusion chromatography small-angle X-ray scattering) experiments, including column equilibration were also implemented. Automatic data processing and analysis are now managed via Dahu, an online server with upstream data reduction, data scaling and azimuthal integration built around PyFAI (Python Fast Azimuthal Integration), and data analysis performed using the open source FreeSAS. The results of this automated data analysis pipeline are displayed in ISPyB/ExiSAXS. The upgraded BM29 has been in operation since the post-EBS restart in September 2020, and here a full description of its new hardware and software characteristics together with examples of data obtained are provided.

Redox-Active Cerium Fluoride Nanoparticles Selectively Modulate Cellular Response against X-ray Irradiation In Vitro.

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells-hMSC) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSC from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in hMSC, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 h after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA-repair system after X-ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of hMSC from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.

Fatal course of a benign mediastinal lipoblastoma in a 20-year-old woman.

Lipoblastoma is a rare benign, but highly proliferative tumor most commonly seen in early childhood. Recurrence rates are high when complete resection is unfeasible and systemic therapy is necessary. We report the case of a large, aggressive thoracic and mediastinal lipoblastoma in a 20-year-old woman, which was surgically not resectable. The tumor has been characterized extensively including molecular pathology, molecular karyotyping, conventional chromosomal analysis and in vitro-chemosensitivity testing in search for alternative therapies. Nevertheless, this did not reveal treatable targets and systemic therapies, which were based on chemosensitivity testing proved ineffective. Despite all treatment attempts, the disease showed a progressive fatal course.

Development and Practical Application of Glucose Biosensor Based on Dendritic Gold Nanostructures Modified by Conducting Polymers.

In this study, graphite rod (GR) electrodes were electrochemically modified by dendritic gold nanostructures (DGNs) followed by immobilization of glucose oxidase (GOx) in the presence of mediator phenazine methosulfate (PMS). Modified with polyaniline (PANI) or polypyrrole (Ppy), GOx/DGNs/GR electrodes were used in glucose biosensor design. Different electrochemical methods were applied for the registration of glucose concentration, and constant potential amperometry (CPA) was chosen as the best one. PANI and Ppy layers synthesized enzymatically on the GOx/DGNs/GR electrodes extended the linear glucose determination range, the width of which depended on the duration of PANI- and Ppy-layers formation. Enzymatically formed polypyrrole was determined as the most suitable polymer for the modification and formation of the glucose biosensor instead of polyaniline, because it was 1.35 times more sensitive and had a 2.57 times lower limit of detection (LOD). The developed glucose biosensor based on the Ppy/GOx/DGNs/GR electrode was characterized by appropriate sensitivity (59.4 µA mM-1 cm-2), low LOD (0.070 mmol L-1), wide linear glucose determination range (up to 19.9 mmol L-1), good repeatability (8.01%), and appropriate storage stability (33 days). The performance of the developed glucose biosensor was tested in biological samples and beverages.

Laser-ablative aqueous synthesis and characterization of elemental boron nanoparticles for biomedical applications.

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.

Synthesis of Titanium Nitride Nanoparticles by Pulsed Laser Ablation in Different Aqueous and Organic Solutions.

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.

Laser Synthesized Core-Satellite Fe-Au Nanoparticles for Multimodal In Vivo Imaging and In Vitro Photothermal Therapy.

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.

Laser-Ablative Synthesis of Ultrapure Magneto-Plasmonic Core-Satellite Nanocomposites for Biomedical Applications.

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.