Репозиторий Университета

© 2020, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature. One dimensional (1D) nanostructures attract considerable attention, enabling a broad application owing to their unique properties. However, the precise mechanism of 1D morphology attainment remains a matter of debate. In this study, ultrafast picosecond (ps) laser-induced treatment on upconversion nanoparticles (UCNPs) is offered as a tool for 1D-nanostructures formation. Fragmentation, reshaping through recrystallization process and bioadaptation of initially hydrophobic (β-Na1.5Y1.5F6: Yb3+, Tm3+/β-Na1.5Y1.5F6) core/shell nanoparticles by means of one-step laser treatment in water are demonstrated. “True” 1D nanostructures through “Medusa”-like structures can be obtained, maintaining anti-Stokes luminescence functionalities. A matter of the one-dimensional UCNPs based on direction of energy migration processes is debated. The proposed laser treatment approach is suitable for fast UCNP surface modification and nano-to-nano transformation, that open unique opportunities to expand UCNP applications in industry and biomedicine. [Figure not available: see fulltext.].

© 2020 This study demonstrates an ultra-sensitive material towards 1-butylamine. The material is composed of 4 wt% Au nanoparticles decorated on MoO3 nanobelts, which are prepared via the hydrothermal method and in-situ reduction. The related characterizations reveal that the nanobelts are highly crystallized layer structures with a width of ~ 200 nm, a thickness of 40 nm and a length of several micrometers. The Au/MoO3 composites exhibit ultra-high sensing response (~300) towards 100 ppm of 1-butylamine at the working temperature of 240 °C. Even without Au decoration, the pristine MoO3 nanobelts offer the response as high as ~ 90 toward the same concentration of 1-butylamine at the temperature of 340 °C, much higher than the existing materials. More importantly, the proposal materials have excellent selectivity towards 1-butylamine, which offers the possibility for practical use. The excellent sensing performance is attributed to the unique sensing mechanism of the layered MoO3 nanobelts via catalytic reaction between 1-butylamine and the lattice oxygen of MoO3. Besides, Au decoration enables to enhance the adsorption of 1-butylamine and facilitate the catalytic sensing process, resulting in further increase in sensing response and selectivity of 1-butylamine. This study may shield light on a promising high-performance gas sensing materials to detect amines in practical application.

© 2020 Biosensors based on nanotechnology are developing rapidly and are widely applied in many fields including biomedicine, environmental monitoring, national defense and analytical chemistry, and have achieved vital positions in these fields. Novel nano-materials are intensively developed and manufactured for potential biosensing and theranostic applications while lacking comprehensive assessment of their potential health risks. The integration of diagnostic in vivo biosensors and the DDSs for delivery of therapeutic drugs holds an enormous potential in next-generation theranostic platforms. Controllable, precise, and safe delivery of diagnostic biosensing devices and therapeutic agents to the target tissues, organs, or cells is an important determinant in developing advanced nanobiosensor-based theranostic platforms. Particularly, inspired by the comprehensive biological investigations on the red blood cells (RBCs), advanced strategies of RBC-mediated in vivo delivery have been developed rapidly and are currently in different stages of transforming from research and design to pre-clinical and clinical investigations. In this review, the RBC-mediated delivery of in vivo nanobiosensors for applications of bio-imaging at the single-cell level, advanced medical diagnostics, and analytical detection of biomolecules and cellular activities are presented. A comprehensive perspective of the technical framework of the state-of-the-art RBC-mediated delivery systems is explained in detail to inspire the design and implementation of advanced nanobiosensor-based theranostic platforms taking advantage of RBC-delivery modalities.

© 2020 Microcapsules are ideal cargo platform for variety of applications such as drug delivery, sensing and imaging due to the combination of a simplicity fabrication and flexibility in the design. We developed remotely collapsing polymer capsules to response to external microwave treatment. The multilayer structure of the capsules was designed to create a polyfunctional system intercalating with nanodiamonds (NDs) and upconversion nanoparticles (UCNPs) into the polyelectrolyte shell. NDs empower local overheating to the microcapsules, while UCNPs provide opportunity to luminescent thermal sensing. UCNPs consist of inorganic crystalline host matrix - hexagonal β-phase NaYF4, doped with pairs of trivalent lanthanide ions, which play role of sensitizer (Yb3+) and activator (Er3+). The microwave triggering followed by the capsule heating results in the controlled destruction of the polyelectrolyte shell with subsequent cargo release. UCNPs luminescence was utilized to determine the local temperature of the capsule shell at nanoscale under GHz ultrasonic treatment. Our novel approach provides on demand microcapsule system destruction, which can be used in the development of nanotheranostic platform for the unification of diagnosis and treatment of various diseases.

© 2020 Elsevier B.V. Fe/Fe3O4 nanoparticles have been deposited on the surfaces of ultrathin CoFeB film and CoFeB/Ta/CoFeB hetero-structure to be detected due to the stray field generated by one particle or a cluster of particles. Exchange biased Fe/Fe3O4 core-shell nanoparticles have been used to stabilize the particles magnetization. Comparison between the Atomic Force and Magnetic Force Microscope images and subtraction of corresponding phase contrasts allows visualization of the film magnetization affected by the particles. Spectra of Ferromagnetic Resonance of the ultrathin films with deposited particles allow one to estimate particle/film dipolar interaction. The results will be useful for the development of lab-on-chip sensors of magnetically labeled cells. Estimation of particles number by magnetic response of the CoFeB heterostructure is demonstrated.

© 2020 Elsevier Inc. Peroxidase nanoenzymes exhibit a specific affinity toward substrates, thereby demonstrating application potential for realizing the colorimetric immunoassays of hydrogen peroxide (H2O2), which can be further used as a probe for imaging cancer cells. To enhance the intrinsic peroxidase activity of molybdenum sulfide (MoS2) nanomaterials, gold (Au) nanoparticles with an average diameter of approximately 2.1 nm were modified on a MoS2/carbon surface (denoted as MoS2/C-Au600) via ascorbic acid reduction. MoS2/C-Au600 can oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to generate a blue oxidation product in the presence of H2O2; this product exhibits peroxidase-like activities, superior to those of most existing MoS2-based nanoenzymes. Furthermore, MoS2/C-Au600 exhibits a high detection capability for H2O2 in the range of 1 × 10−5 to 2 × 10−4 mol/L (R2 = 0.99), and the lowest detection limit is 1.82 µmol/L in a sodium acetate and acetic acid buffer solution. Steady state kinetics studies indicate that the catalytic mechanism is consistent with the ping-pong mechanism. Given its strong absorption peak at 652 nm in the visible region, MoS2/C-Au600 can be used to image cancer cells due to the enhanced permeability and retention effect. Our findings demonstrate that the synergistic electronic coupling between multiple components can enhance the peroxidase activity, which can facilitate the development of an effective, facile, and reliable method to perform colorimetric immunoassays of H2O2 and cancer cells.

© 2020 Elsevier Inc. This study reports the differences in toxic action between cadmium sulfide (CdS) and zinc sulfide (ZnS) nanoparticles (NPs) prepared by recently developed xanthate-mediated method. The aquatic toxicity of the synthesized NPs on four marine microalgae species was explored. Growth rate, esterase activity, membrane potential, and morphological changes of microalgae cells were evaluated using flow cytometry and optical microscopy. CdS and ZnS NPs demonstrated similar level of general toxicity and growth-rate inhibition to all used microalgae species, except the red algae P. purpureum. More specifically, CdS NPs caused higher inhibition of growth rate for C. muelleri and P. purpureum, while ZnS NPs were more toxic for A. ussuriensis and H. akashiwo species. Our findings suggest that the sensitivity of different microalgae species to CdS and ZnS NPs depends on the chemical composition of NPs and their ability to interact with the components of microalgal cell-wall. The red microalga was highly resistant to ZnS NPs most likely due to the presence of phycoerythrin proteins in the outer membrane bound Zn2+ cations defending their cells from further toxic influence. The treatment with CdS NPs caused morphological changes and biochemical disorder in all tested microalgae species. The toxicity of CdS NPs is based on their higher photoactivity under visible light irradiation and lower dissociation in water, which allows them to generate more reactive oxygen species and create a higher risk of oxidative stress to aquatic organisms. The results of this study contribute to our understanding of the parameters affecting the aquatic toxicity of semiconductor NPs and provide a basis for further investigations.

© 2020 Elsevier Inc. This study reports the differences in toxic action between cadmium sulfide (CdS) and zinc sulfide (ZnS) nanoparticles (NPs) prepared by recently developed xanthate-mediated method. The aquatic toxicity of the synthesized NPs on four marine microalgae species was explored. Growth rate, esterase activity, membrane potential, and morphological changes of microalgae cells were evaluated using flow cytometry and optical microscopy. CdS and ZnS NPs demonstrated similar level of general toxicity and growth-rate inhibition to all used microalgae species, except the red algae P. purpureum. More specifically, CdS NPs caused higher inhibition of growth rate for C. muelleri and P. purpureum, while ZnS NPs were more toxic for A. ussuriensis and H. akashiwo species. Our findings suggest that the sensitivity of different microalgae species to CdS and ZnS NPs depends on the chemical composition of NPs and their ability to interact with the components of microalgal cell-wall. The red microalga was highly resistant to ZnS NPs most likely due to the presence of phycoerythrin proteins in the outer membrane bound Zn2+ cations defending their cells from further toxic influence. The treatment with CdS NPs caused morphological changes and biochemical disorder in all tested microalgae species. The toxicity of CdS NPs is based on their higher photoactivity under visible light irradiation and lower dissociation in water, which allows them to generate more reactive oxygen species and create a higher risk of oxidative stress to aquatic organisms. The results of this study contribute to our understanding of the parameters affecting the aquatic toxicity of semiconductor NPs and provide a basis for further investigations.

© 2019 Elsevier B.V. Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30–70 kDa with a presumably safer low molecular mass PVA 9–10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.

© 2019 Elsevier B.V. Due to their unique optical properties upconversion nanoparticles (UCNPs) provide exceptionally high contrast for imaging of true nanoparticle distribution in excised human skin. It makes possible to show penetration of solid nanoparticles in skin treated with chemical enhancers. We demonstrated tracing upconversion nanoparticles in excised human skin by means of optical microscopy at the discrete particle level sensitivity to obtain their penetration profiles, which was validated by laser-ablation inductively-coupled-plasma mass-spectrometry. To demonstrate utilities of our method, UCNPs were coated with polymers, formulated in water and chemical enhancers, and applied on excised human skin mounted on Franz cells, followed by imaging using a custom-built laser-scanning microscope. To evaluate the toxicity impact on skin by polymer-coated UCNPs, we introduced a tissue engineering model of viable epidermis made of decellularized chick embryo skin seeded with keratinocytes. UCNPs formulated in water stopped in stratum corneum, whereas UCNPs formulated in ethanol-water solution crossed stratum corneum and reached viable epidermis – hence, the enhancement effect for solid nanoparticles was detected by optical microscopy. All polymer-coated UCNPs were found nontoxic within the accepted safety levels. The keratinocyte resilience to polyethyleneimine-coated UCNPs was surprising considering cytotoxicity of polyethyleneimine to two-dimensional cell cultures.

© 2019 Elsevier B.V. SERS substrate containing SERS-active array of Ag, Au and Ag50Au50 nanoparticles with normal size distribution, a mirror layer and a separating SiO2 layer was optimized. A layer of amorphous carbon was used as the object of study. It is shown that such a structure enhances the Raman signal both due to the localized surface plasmon resonance and due to interference. The average size of nanoparticles, the reflection coefficient of mirror layer, and the thickness of SiO2 layer influence the amplification of the Raman signal. To provide amplification the thickness of SiO2 layer should be calculated for the appropriate wavelength in order to get constructive interference. It is revealed that additional amplification of the Raman signal occurs if the mirror layer as well as the array of particles is made of plasmon metal and thickness of separating SiO2 layer is quite small (up to 30 nm).

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Human serum albumin nanoparticles (HSA-NPs) have been widely used as drug delivery systems. In most cases, HSA-NPs are formed by the method of desolvation in the presence of glutaraldehyde as a crosslinking agent. In the present study, we showed the possibility of crosslinking human serum albumin (HSA) molecules with natural agents, urea, and cysteine at the nanoparticle level under mild conditions (at room temperature of 20–25 °C). Optimal concentrations of the interacting components (HSA, urea, and cysteine) were found to produce nanoparticles with optimal physico-chemical parameters (particle size, polydispersity, zeta potential, yield, etc.) for application as drug carriers. We used hydroxyurea (HU), a simple organic compound currently used as a cancer chemotherapeutic agent. The results indicated sizes of 196 ± 5 nm and 288 ± 10 nm with a surface charge of −22 ± 3.4 mV and −17.4 ± 0.5 mV for HSA-NPs (20 mg/mL of HSA, 0.01 mg/mL of cysteine, and 10 mg/mL of urea) and HSA–HU-NPs (2 mg/mL of HU), respectively. The yield of the HSA–HU-NPs was ~93% with an encapsulation efficiency of ~77%. Thus, the particles created (immobilized with HU) were stable over time and able to prolong the effect of the drug.

© 2019 American Pharmacists Association® Various drug delivery systems (DDSs) are often used in modern medicine to achieve controlled and targeted drug release. Diffusional release of drugs from DDSs is often the main mechanism, especially at early times. Generally, average dimensions of DDS are used to model the drug release, but our recent work on drug release from fibers demonstrated that taking into account diameter distribution is essential. This work systematically investigated the effect of size distribution on diffusional drug release from DDSs of various geometric forms such as membranes, fibers, and spherical particles. The investigation clearly demonstrated that the size distribution has the largest effect on the drug release profiles from spherical particles compared to other geometric forms. Published experimental data for drug release from polymer microparticles and nanoparticles were fitted, and the diffusion coefficients were determined assuming reported radius distributions. Assuming the average radius when fitting the data leads to up to 5 times underestimation of the diffusion coefficient of drug in the polymer.

© 2018 National Academy of Sciences. All rights reserved. We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R-T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2 receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T distribution in cells and animals. Specific binding and uptake of UCNP complexes in SK-BR-3 cells was observed, with separate 90Y- and PE40-induced cytotoxic effects characterized by IC50 140 μg/mL (UCNP-R) and 5.2 μg/mL (UCNP-T), respectively. When both therapeutic agents were combined into UCNP-R-T, the synergetic effect increased markedly, ∼2200-fold, resulting in IC50 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.

Copyright © 2018 American Chemical Society. Upconversion nanoparticles (UCNPs) coated with polyethylenimine (PEI) are popular background-free optical contrast probes and efficient drug and gene delivery agents attracting attention in science, industry, and medicine. Their unique optical properties are especially useful for subsurface nanotheranostics applications, in particular, in skin. However, high cytotoxicity of PEI limits safe use of UCNP@PEI, and this represents a major barrier for clinical translation of UCNP@PEI-based technologies. Our study aims to address this problem by exploring additional surface modifications to UCNP@PEI to create less toxic and functional nanotheranostic materials. We designed and synthesized six types of layered polymer coatings that envelop the original UCNP@PEI surface, five of which reduced the cytotoxicity to human skin keratinocytes under acute (24 h) and subacute (120 h) exposure. In parallel, we examined the photoluminescence spectra and lifetime of the surface-modified UCNP@PEI. To quantify their brightness, we developed original methodology to precisely measure the colloidal concentration to normalize the photoluminescence signal using a nondigesting mass spectrometry protocol. Our results, specified for the individual coatings, show that, despite decreasing the cytotoxicity, the external polymer coatings of UCNP@PEI quench the upconversion photoluminescence in biologically relevant aqueous environments. This trade-off between cytotoxicity and brightness for surface-coated UCNPs emphasizes the need for the combined assessment of the viability of normal cells exposed to the nanoparticles and the photophysical properties of postmodification UCNPs. We present an optimized methodology for rational surface design of UCNP@PEI in biologically relevant conditions, which is essential to facilitate the translation of such nanoparticles to the clinical applications.

© 2018 Society of Photo-Optical Instrumentation Engineers (SPIE). We present the nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography (OCT). It employs an experimental training algorithm based on imaging of a test-object, made of the colloidal suspension of the monodisperse nanoparticles and contains the microscale inclusions. The geometry and the scattering properties of the test-object are known a priori allowing us to set the criteria for the training algorithm. Using a wide set of the wavelet kernels and the wavelet-domain filtration approaches, the appropriate filter is constructed based on the test-object imaging. We apply the proposed approach and chose an efficient wavelet denoising procedure by considering the combinations of the decomposition basis from five wavelet families with eight types of the filtration threshold. We demonstrate applicability of the wavelet-filtering for the in vitro OCT image of human brain meningioma. The observed results prove high efficiency of the proposed OCT image denoising technique.

© 2018 Elsevier B.V. Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature.  We studied the influence of magnetite nanoparticles (FeO•Fe 2 O 3 ) and quantum dots (CdSe/ZnS coated with mercaptopropionic acid) on the expression of 5 common reference genes (BA, B2M, PPIA, UBC, and YWHAZ) in peripheral blood cells from 20 volunteers by reverse transcription PCR method. The stability of the expression of reference genes varied depending of the cells type and chemical structure of nanoparticles. The level of YWHAZ mRNA after exposure by nanoparticles demonstrated highest stability in lymphocytes, neutrophils, and monocytes. Stability of YWHAZ expression was confirmed by Western blotting. Our findings suggest that YWHAZ is the most suitable as the reference gene.

© 2018 Istituto Superiore di Sanita. All Rights Reserved. Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.

© 2018 Trans Tech Publications, Switzerland  This paper presents the results of experimental studies of arrays of Ag 0.52 Au 0.48 alloy nanoparticles. Arrays were formed by vacuum-thermal evaporation on an unheated substrate and subsequent low-temperature vacuum annealing. The TEM images of the obtained nanoparticle arrays and corresponding histograms of particle size distribution are shown. The transmission spectra of these arrays showing the displacement of the plasma frequency as a function of the mean particle size are obtained. Spectra of Raman scattering from a thin film of amorphous carbon in presence of AgAu particles are obtained, and a comparative analysis of Raman scattering amplification factors for pure Ag, pure Au and Ag 0.52 Au 0.48 alloy nanoparticles is presented.