Electrochemical real-time sensor for the detection of Pb(II) ions based on Ti3C2Tx MXene.

Lead ions are especially harmful to human health, causing significant developmental and behavioral abnormalities even at small concentrations. In real-life samples, lead ions are present in mixtures with other metal ions, creating a challenge to detect it selectively at low quantities. To address these challenges, we prepared an electrochemical sensor based on delaminated Ti3C2Tx MXene, which can selectively detect low concentrations of Pb2+ in a solution containing other common metal ions. Cyclic voltammetry was applied as an electrochemical detection method. The proposed reaction mechanism involves a reversible transition between Pb2+ ions and PbO at the MXene-based layer. The sensitivity of the sensor towards Pb2+ ions and a limit of detection were determined. The sensor, as prepared, had a linear response range within 0.15-1.0 µM, with a sensitivity of 26.7 µA/µM and LOD value of 48.7 nM, which meets the requirements set by the World Health Organization.

Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization.

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.

Surface Plasmon Resonance Immunosensor for Direct Detection of Antibodies against SARS-CoV-2 Nucleocapsid Protein.

The strong immunogenicity of the SARS-CoV-2 nucleocapsid protein is widely recognized, and the detection of specific antibodies is critical for COVID-19 diagnostics in patients. This research proposed direct, label-free, and sensitive detection of antibodies against the SARS-CoV-2 nucleocapsid protein (anti-SCoV2-rN). Recombinant SARS-CoV-2 nucleocapsid protein (SCoV2-rN) was immobilized by carbodiimide chemistry on an SPR sensor chip coated with a self-assembled monolayer of 11-mercaptoundecanoic acid. When immobilized under optimal conditions, a SCoV2-rN surface mass concentration of 3.61 ± 0.52 ng/mm2 was achieved, maximizing the effectiveness of the immunosensor for the anti-SCoV2-rN determination. The calculated KD value of 6.49 × 10-8 ± 5.3 × 10-9 M confirmed the good affinity of the used monoclonal anti-SCoV2-rN antibodies. The linear range of the developed immunosensor was from 0.5 to 50 nM of anti-SCoV2-rN, where the limit of detection and the limit of quantification values were 0.057 and 0.19 nM, respectively. The immunosensor exhibited good reproducibility and specificity. In addition, the developed immunosensor is suitable for multiple anti-SCoV2-rN antibody detections.

Postural control in gymnasts: anisotropic fractal scaling reveals proprioceptive reintegration in vestibular perturbation.

Dexterous postural control subtly complements movement variability with sensory correlations at many scales. The expressive poise of gymnasts exemplifies this lyrical punctuation of release with constraint, from coarse grain to fine scales. Dexterous postural control upon a 2D support surface might collapse the variation of center of pressure (CoP) to a relatively 1D orientation-a direction often oriented towards the focal point of a visual task. Sensory corrections in dexterous postural control might manifest in temporal correlations, specifically as fractional Brownian motions whose differences are more and less correlated with fractional Gaussian noises (fGns) with progressively larger and smaller Hurst exponent H. Traditional empirical work examines this arrangement of lower-dimensional compression of CoP along two orthogonal axes, anteroposterior (AP) and mediolateral (ML). Eyes-open and face-forward orientations cultivate greater variability along AP than ML axes, and the orthogonal distribution of spatial variability has so far gone hand in hand with an orthogonal distribution of H, for example, larger in AP and lower in ML. However, perturbing the orientation of task focus might destabilize the postural synergy away from its 1D distribution and homogenize the temporal correlations across the 2D support surface, resulting in narrower angles between the directions of the largest and smallest H. We used oriented fractal scaling component analysis (OFSCA) to investigate whether sensory corrections in postural control might thus become suborthogonal. OFSCA models raw 2D CoP trajectory by decomposing it in all directions along the 2D support surface and fits the directions with the largest and smallest H. We studied a sample of gymnasts in eyes-open and face-forward quiet posture, and results from OFSCA confirm that such posture exhibits the classic orthogonal distribution of temporal correlations. Head-turning resulted in a simultaneous decrease in this angle Δθ, which promptly reversed once gymnasts reoriented their heads forward. However, when vision was absent, there was only a discernible negative trend in Δθ, indicating a shift in the angle's direction but not a statistically significant one. Thus, the narrowing of Δθ may signify an adaptive strategy in postural control. The swift recovery of Δθ upon returning to a forward-facing posture suggests that the temporary reduction is specific to head-turning and does not impose a lasting burden on postural control. Turning the head reduced the angle between these two orientations, facilitating the release of postural degrees of freedom towards a more uniform spread of the CoP across both dimensions of the support surface. The innovative aspect of this work is that it shows how fractality might serve as a control parameter of adaptive mechanisms of dexterous postural control.

Monitoring Ti3C2Tx MXene Degradation Pathways Using Raman Spectroscopy.

Extending applications of Ti3C2Tx MXene in nanocomposites and across fields of electronics, energy storage, energy conversion, and sensor technologies necessitates simple and efficient analytical methods. Raman spectroscopy is a critical tool for assessing MXene composites; however, high laser powers and temperatures can lead to the materials' deterioration during the analysis. Therefore, an in-depth understanding of MXene photothermal degradation and changes in its oxidation state is required, but no systematic studies have been reported. The primary aim of this study was to investigate the degradation of the MXene lattice through Raman spectroscopic analysis. Distinct spectral markers were related to structural alterations within the Ti3C2Tx material after subjecting it to thermal- and laser-induced degradation. During the degradation processes, spectral markers were revealed for several specific steps: a decrease in the number of interlayer water molecules, a decrease in the number of -OH groups, formation of C-C bonds, oxidation of the lattice, and formation of TiO2 nanoparticles (first anatase, followed by rutile). By tracking of position shifts and intensity changes for Ti3C2Tx, the spectral markers that signify the initiation of each step were found. This spectroscopic approach enhances our understanding of the degradation pathways of MXene, and facilitating enhanced and dependable integration of these materials into devices for diverse applications, from energy storage to sensors.

Gadolinium Doping Modulates the Enzyme-like Activity and Radical-Scavenging Properties of CeO2 Nanoparticles.

Their unique physicochemical properties and multi-enzymatic activity make CeO2 nanoparticles (CeO2 NPs) the most promising active component of the next generation of theranostic drugs. When doped with gadolinium ions, CeO2 NPs constitute a new type of contrast agent for magnetic resonance imaging, possessing improved biocatalytic properties and a high level of biocompatibility. The present study is focused on an in-depth analysis of the enzyme-like properties of gadolinium-doped CeO2 NPs (CeO2:Gd NPs) and their antioxidant activity against superoxide anion radicals, hydrogen peroxide, and alkylperoxyl radicals. Using an anion-exchange method, CeO2:Gd NPs (~5 nm) with various Gd-doping levels (10 mol.% or 20 mol.%) were synthesized. The radical-scavenging properties and biomimetic activities (namely SOD- and peroxidase-like activities) of CeO2:Gd NPs were assessed using a chemiluminescent method with selective chemical probes: luminol, lucigenin, and L-012 (a highly sensitive luminol analogue). In particular, gadolinium doping has been shown to enhance the radical-scavenging properties of CeO2 NPs. Unexpectedly, both bare CeO2 NPs and CeO2:Gd NPs did not exhibit SOD-like activity, acting as pro-oxidants and contributing to the generation of reactive oxygen species. Gadolinium doping caused an increase in the pro-oxidant properties of nanoscale CeO2. At the same time, CeO2:Gd NPs did not significantly inhibit the intrinsic activity of the natural enzyme superoxide dismutase, and CeO2:Gd NPs conjugated with SOD demonstrated SOD-like activity. In contrast to SOD-like properties, peroxidase-like activity was observed for both bare CeO2 NPs and CeO2:Gd NPs. This type of enzyme-like activity was found to be pH-dependent. In a neutral medium (pH = 7.4), nanoscale CeO2 acted as a prooxidant enzyme (peroxidase), while in an alkaline medium (pH = 8.6), it lost its catalytic properties; thus, it cannot be regarded as a nanozyme. Both gadolinium doping and conjugation with a natural enzyme were shown to modulate the interaction of CeO2 NPs with the key components of redox homeostasis.

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.

Magmatism controls global oceanic transform fault topography.

Oceanic transform faults play an essential role in plate tectonics. Yet to date, there is no unifying explanation for the global trend in broad-scale transform fault topography, ranging from deep valleys to shallow topographic highs. Using three-dimensional numerical models, we find that spreading-rate dependent magmatism within the transform domain exerts a first-order control on the observed spectrum of transform fault depths. Low-rate magmatism results in deep transform valleys caused by transform-parallel tectonic stretching; intermediate-rate magmatism fully accommodates far-field stretching, but strike-slip motion induces across-transform tension, producing transform strength dependent shallow valleys; high-rate magmatism produces elevated transform zones due to local compression. Our models also address the observation that fracture zones are consistently shallower than their adjacent transform fault zones. These results suggest that plate motion change is not a necessary condition for reproducing oceanic transform topography and that oceanic transform faults are not simple conservative strike-slip plate boundaries.

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.

Older adults and individuals with Parkinson's disease control posture along suborthogonal directions that deviate from the traditional anteroposterior and mediolateral directions.

A rich and complex temporal structure of variability in postural sway characterizes healthy and adaptable postural control. However, neurodegenerative disorders such as Parkinson's disease, which often manifest as tremors, rigidity, and bradykinesia, disrupt this healthy variability. This study examined postural sway in young and older adults, including individuals with Parkinson's disease, under different upright standing conditions to investigate the potential connection between the temporal structure of variability in postural sway and Parkinsonism. A novel and innovative method called oriented fractal scaling component analysis was employed. This method involves decomposing the two-dimensional center of pressure (CoP) planar trajectories to pinpoint the directions associated with minimal and maximal temporal correlations in postural sway. As a result, it facilitates a comprehensive assessment of the directional characteristics within the temporal structure of sway variability. The results demonstrated that healthy young adults control posture along two orthogonal directions closely aligned with the traditional anatomical anteroposterior (AP) and mediolateral (ML) axes. In contrast, older adults and individuals with Parkinson's disease controlled posture along suborthogonal directions that significantly deviate from the AP and ML axes. These findings suggest that the altered temporal structure of sway variability is evident in individuals with Parkinson's disease and underlies postural deficits, surpassing what can be explained solely by the natural aging process.

The effect of gold nanostructure morphology on label-free electrochemical immunosensor design.

In this research, various electrodeposition techniques were used to form gold nanostructures (AuNSs) on the surface of graphite rod electrode (GE). Three distinct AuNS morphologies on GE have been achieved based on the composition of electrodeposition solution. The use of H2SO4 as a supporting electrolyte resulted in the formation of smaller but more numerous AuNSI with a modified electrode's electroactive surface area (EASA) of 0.213 cm2. Exchanging the supporting electrolyte to KNO3 and increasing HAuCl4 concentration facilitated the formation of bigger AuNSII particles with electrode EASA of 0.116 cm2. Finally, a partial coverage of GE by branched gold nanostructures (AuNSIII) was achieved with an estimated EASA of 0.110 cm2, when the HAuCl4 and KNO3 concentrations were increased further. Estimated values of heterogeneous electron transfer rate constant did not depend on AuNS morphology. Electrode modified with AuNSI exhibited the highest bovine serum albumin (BSA) immobilization efficiency and the highest relative response for the detection of specific polyclonal antibodies against BSA (p-anti-BSA) compared to other modified electrodes. The limit of p-anti-BSA detection in PBS buffer was calculated as 0.63 nM, while in blood serum it was 0.71 nM. Linear ranges were from 1 to 7 nM and from 1 to 5 nM, respectively.

Special Issue "Immunoanalytical and Bioinformatics Methods in Immunology Research".

To effectively control and prevent diseases on a global scale, it is essential to employ precise, sensitive, selective, and rapid immunoanalytical methods [...].

ZnO nanostructures: A promising frontier in immunosensor development.

This review addresses the design of immunosensors, which employ ZnO nanostructures. Various methods of modifying ZnO nanostructures with antibodies or antigens are discussed, including covalent and non-covalent approaches and cross-linking techniques. Immunosensors based on different properties of ZnO nanomaterials are described and compared. This article provides a comprehensive review of electrochemical immunosensors based on ZnO nanostructures and various detection techniques, including cyclic voltammetry (CV), differential pulse voltammetry (DPV), photoelectrochemical (PEC) detection, electrochemical impedance spectroscopy (EIS), and other electrochemical methods. In addition, this review article examines the application of optical detection techniques, including photoluminescence (PL) and electrochemiluminescence (ECL), in the development of immunosensors based on ZnO nanostructures.

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.

The Development of Reagentless Amperometric Glucose Biosensor Based on Gold Nanostructures, Prussian Blue and Glucose Oxidase.

Precise blood glucose detection plays a crucial role in diagnosing and medicating diabetes, in addition to aiding diabetic patients in effectively managing their condition. In this research, a first-generation reagentless amperometric glucose biosensor was developed by combining the graphite rod (GR) electrode modification by gold nanostructures (AuNS) and Prussian blue (PB) with glucose oxidase (GOx)-an enzyme that can oxidize glucose and produce H2O2. Firstly, AuNS was electrochemically deposited on the GR electrode (AuNS/GR), and then PB was electrochemically synthesized on the AuNS/GR electrode (PB/AuNS/GR). Finally, GOx was immobilized over the PB/AuNS nanocomposite with the assistance of Nafion (Nf) (Nf-GOx/PB/AuNS/GR). An application of PB in the design of a glucose biosensor enables an easy electrochemical reduction and, thus, the determination of the H2O2 produced during the GOx-catalyzed oxidation of glucose in the sample at a low operation potential of -0.05 V vs. Ag/AgCl/KCl3 mol L-1. In addition, AuNS increased the electrochemically active surface area, improved the GOx immobilization and ensured a higher analytical signal. The developed glucose biosensor based on the Nf-GOx/PB/AuNS/GR electrode exhibited a wide linear range, from 0.025 to 1 mmol L-1 of glucose, with a 0.0088 mmol L-1 limit of detection, good repeatability and high selectivity over electroactive interfering substances. The developed biosensor is convenient for the determination of glucose in the physiological environment.

Synergistic Antimicrobial Effect of Cold Atmospheric Plasma and Redox-Active Nanoparticles.

Cold argon plasma (CAP) and metal oxide nanoparticles are well known antimicrobial agents. In the current study, on an example of Escherichia coli, a series of analyses was performed to assess the antibacterial action of the combination of these agents and to evaluate the possibility of using cerium oxide and cerium fluoride nanoparticles for a combined treatment of bacterial diseases. The joint effect of the combination of cold argon plasma and several metal oxide and fluoride nanoparticles (CeO2, CeF3, WO3) was investigated on a model of E. coli colony growth on agar plates. The mutagenic effect of different CAP and nanoparticle combinations on bacterial DNA was investigated, by means of a blue-white colony assay and RAPD-PCR. The effect on cell wall damage, using atomic force microscopy, was also studied. The results obtained demonstrate that the combination of CAP and redox-active metal oxide nanoparticles (RAMON) effectively inhibits bacterial growth, providing a synergistic antimicrobial effect exceeding that of any of the agents alone. The combination of CAP and CeF3 was shown to be the most effective mutagen against plasmid DNA, and the combination of CAP and WO3 was the most effective against bacterial genomic DNA. The analysis of direct cell wall damage by atomic force microscopy showed the combination of CAP and CeF3 to be the most effective antimicrobial agent. The combination of CAP and redox-active metal oxide or metal fluoride nanoparticles has a strong synergistic antimicrobial effect on bacterial growth, resulting in plasmid and genomic DNA damage and cell wall damage. For the first time, a strong antimicrobial and DNA-damaging effect of CeF3 nanoparticles has been demonstrated.

Influence of the Synthesis Scheme of Nanocrystalline Cerium Oxide and Its Concentration on the Biological Activity of Cells Providing Wound Regeneration.

In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to evaluate the effect of different concentrations of nanoceria (from 10-2 to 10-6 M) on cells involved in the regeneration of skin cell structures such as fibroblasts, mesenchymal stem cells, and keratinocytes. Two different methods of nanoceria preparation were investigated: (1) CeO-NPs-1 by precipitation from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid and (2) CeO-NPs-2 by hydrolysis of ammonium hexanitratocerate (IV) under conditions of thermal autoclaving. According to the X-ray diffraction, transmission electron microscopy, and dynamic light scattering data, CeO2-1 consists of individual particles of cerium dioxide (3-5 nm) and their aggregates with diameters of 60-130 nm. CeO2-2 comprises small aggregates of 8-20 nm in diameter, which consist of particles of 2-3 nm in size. Cell cultures of human fibroblasts, human mesenchymal stem cells, and human keratinocytes were cocultured with different concentrations of nanoceria sols (10-2, 10-3, 10-4, 10-5, and 10-6 mol/L). The metabolic activity of all cell types was investigated by MTT test after 48 and 72 h, whereas proliferative activity and cytotoxicity were determined by quantitative cell culture counting and live/dead test. A dependence of biological effects on the method of nanoceria preparation and concentration was revealed. Data were obtained with respect to the optimal concentration of sol to achieve the highest metabolic effect in the used cell cultures. Hypotheses about the mechanisms of the obtained effects and the structure of a fundamentally new medical device for accelerated healing of skin wounds were formulated. The method of nanoceria synthesis and concentration fundamentally and significantly change the biological activity of cell cultures of different types-from suppression to pronounced stimulation. The best biological activity of cell cultures was determined through cocultivation with sols of citrate nanoceria (CeO-NPs-1) at a concentration of 10-3-10-4 M.

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.