Nanotechnology, Science and Applications最新文献

[This retracts the article DOI: 10.2147/NSA.S266663.].

Controlled and contactless movements of magnetic nanoparticles are crucial for fundamental biotechnological and clinical research (eg, cell manipulation and sorting, hyperthermia, and magnetic drug targeting). However, the key technological question, how to generate suitable magnetic fields on various length scales (µm-m), is still unsolved. Here, we present a system of permanent magnets which allows for steering of iron oxide nanoparticles (SPIONs) on arbitrary trajectories observable by microscopy. The movement of the particles is simply controlled by an almost force-free rotation of cylindrical arrangements of permanent magnets. The same instrument can be used to move suspended cells loaded with SPIONs along with predetermined directions. Surprisingly, it also allows for controlled movements of intracellular compartments inside of individual cells. The exclusive use of permanent magnets simplifies scaled up versions for animals or even humans, which would open the door for remotely controlled in vivo guidance of nanoparticles or micro-robots.

Introduction: Functionalization of water-soluble chitosan (WSCS) nanocolloids with, gold nanoparticles (AuNPs), and LyslLys3 (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-bombesin 1-14 (DOTA-BBN) peptide affords an innovative pathway to produce prostate tumor cell-specific nanomedicine agents with potential applications in molecular imaging and therapy.

Methods: The preparation involves the production and full characterization of water-soluble chitosan (WSCS), via gamma (γ) rays (80 kGy) irradiation, followed by DOTA-BBN conjugation for subsequent use as an effective template toward the synthesis of tumor cell-specific AuNPs-WSCS-DOTA-BBN.

Results: The WSCS-DOTA-BBN polymeric nanoparticles (86 ± 2.03 nm) served multiple roles as reducing and stabilizing agents in the overall template synthesis of tumor cell-targeted AuNPs. The AuNPs capped with WSCS and WSCS-DOTA-BBN exhibited average Au-core diameter of 17 ± 8 nm and 20 ± 7 nm with hydrodynamic diameters of 56 ± 1 and 67± 2 nm, respectively. The AuNPs-WSCS-DOTA-BBN showed optimum in vitro stability in biologically relevant solutions. The targeted AuNPs showed selective affinity toward GRP receptors overexpressed in prostate cancer cells (PC-3 and LNCaP).

Discussion: The AuNPs-WSCS-DOTA-BBN displayed cytotoxicity effects against PC-3 and LNCaP cancer cells, with concomitant safety toward the HAECs normal cells. The AuNPs-WSCS-DOTA-BBN showed synergistic targeting toward tumor cells with selective cytotoxicity of AuNPs towards PC-3 and LNCaP cells. Our investigations provide compelling evidence that AuNPs functionalized with WSCS-DOTA-BBN is an innovative nanomedicine approach for use in molecular imaging and therapy of GRP receptor-positive tumors. The template synthesis of AuNPs-WSCS-DOTA-BBN serves as an excellent non-radioactive surrogate for the development of the corresponding ¹⁹⁸AuNPs theragnostic nanoradiopharmaceutical for use in cancer diagnosis and therapy.

Introduction: Oxidative tissue damage caused by reactive oxygen species results in a significant decrease in the total antioxidant capacity of the biological system. The aim of this interdisciplinary study was to answer the question of whether active antioxidants modify, at a molecular and supramolecular level, the tissue of pathological amnion and the necrotic eschar degraded in thermal burn.

Methods: A Nicolet 6700 Fourier-transform spectrophotometer with OMNIC software and the EasiDiff diffusion accessory were used in the FTIR spectroscopic analysis. A NICOLET MAGNA-IR 860 spectrometer with FT-Raman accessory was used to record the Raman spectra of the samples. The samples were exposed to bacteria capable of causing nosocomial infections, ie Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa. Whereas samples of hypotrophic amnion interacted with Staphylococcus aureus, Escherichia coli and Enterococcus faecalis. The obtained flame retardant effect of placentas was evaluated using the method of the limiting oxygen index (LOI).

Results: The infrared spectroscopy analysis proved that after modification of the amniotic samples in graphene oxide and ortho-silicic acid, the amide II band is split into two components. Incubation of samples in modifier solutions: graphene oxide, sodium ascorbate and L-ascorbic acid results in shifts and changes of intensity within the broadly understood lipid band 1743-1745-1747 cm^-1. The oxidising changes observed within the lipid and amide bands are affected by the incubation effect of graphene oxide as a modifier, possibly adsorbing on the surface of the amniotic membrane. On the basis of microbiological studies, pathogenic bacteria commonly causing amniotic infections and growing in burn wounds were found to have particularly good resistance to stabilized ortho-silicic acid (E. coli) and lactoferrin (S.aureus).

Conclusion: This thermogravimetric study found the highest stability of the analysed tissues (hypotrophic amnion and burnt epidermis) after modification with graphene oxide and sodium ascorbate.

Introduction: Since most biologically active macromolecules are natural nanostructures, operating in the same scale of biomolecules gives the great advantage to enhance the interaction with cellular components. Noteworthy efforts in nanotechnology, particularly in biomedical and pharmaceutical fields, have propelled a high number of studies on the biological effects of nanomaterials. Moreover, the determination of specific physicochemical properties of nanomaterials is crucial for the evaluation and design of novel safe and efficient therapeutics and diagnostic tools. In this in vitro study, we report a physicochemical characterisation of fluorescent silica nanoparticles (NPs), interacting with biological models (U937 and PBMC cells), describing the specific triggered biologic response.

Methods: Flow Cytometric and Confocal analyses are the main method platforms. However TEM, NTA, DLS, and chemical procedures to synthesize NPs were employed.

Results: NT_B700 NPs, employed in this study, are fluorescent core-shell silica nanoparticles, synthesized through a micelle-assisted method, where the fluorescence energy transfer process, known as FRET, occurs at a high efficiency rate. Using flow cytometry and confocal microscopy, we observed that NT_B700 NP uptake seemed to be a rapid, concentration-, energy- and cell type-dependent process, which did not induce significant cytotoxic effects. We did not observe a preferred route of internalization, although their size and the possible aggregated state could influence their extrusion. At this level of analysis, our investigation focuses on lysosome and mitochondria pathways, highlighting that both are involved in NP co-localization. Despite the main mitochondria localization, NPs did not induce a significant increase of intracellular ROS, known inductors of apoptosis, during the time course of analyses. Finally, both lymphoid and myeloid cells are able to release NPs, essential to their biosafety.

Discussion: These data allow to consider NT_B700 NPs a promising platform for future development of a multifunctional system, by combining imaging and localized therapeutic applications in a unique tool.

Purpose: AntiOxCIN₃ is a novel mitochondriotropic antioxidant developed to minimize the effects of oxidative stress on neurodegenerative diseases. Prior to an investment in pre-clinical in vivo studies, it is important to apply in silico and biophysical cell-free in vitro studies to predict AntiOxCIN₃ biodistribution profile, respecting the need to preserve animal health in accordance with the EU principles (Directive 2010/63/EU). Accordingly, we propose an innovative toolbox of biophysical studies and mimetic models of biological interfaces, such as nanosystems with different compositions mimicking distinct membrane barriers and human serum albumin (HSA).

Methods: Intestinal and cell membrane permeation of AntiOxCIN₃ was predicted using derivative spectrophotometry. AntiOxCIN₃ -HSA binding was evaluated by intrinsic fluorescence quenching, synchronous fluorescence, and dynamic/electrophoretic light scattering. Steady-state and time-resolved fluorescence quenching was used to predict AntiOxCIN₃-membrane orientation. Fluorescence anisotropy, synchrotron small- and wide-angle X-ray scattering were used to predict lipid membrane biophysical impairment caused by AntiOxCIN₃ distribution.

Results and discussion: We found that AntiOxCIN₃ has the potential to permeate the gastrointestinal tract. However, its biodistribution and elimination from the body might be affected by its affinity to HSA (>90%) and by its steady-state volume of distribution (VD_SS =1.89± 0.48 L∙Kg^-1). AntiOxCIN₃ is expected to locate parallel to the membrane phospholipids, causing a bilayer stiffness effect. AntiOxCIN₃ is also predicted to permeate through blood-brain barrier and reach its therapeutic target - the brain.

Conclusion: Drug interactions with biological interfaces may be evaluated using membrane model systems and serum proteins. This knowledge is important for the characterization of drug partitioning, positioning and orientation of drugs in membranes, their effect on membrane biophysical properties and the study of serum protein binding. The analysis of these interactions makes it possible to collect valuable knowledge on the transport, distribution, accumulation and, eventually, therapeutic impact of drugs which may aid the drug development process.

Purpose: Magnetotransport properties of granular oxide-segregated CoPtCr films were studied on both macroscopic and microscopic length scales by performing bulk and point-contact magnetoresistance measurements, respectively. Such a perpendicular magnetic medium is used in state-of-the-art hard disc drives and, when combined with magnetotransport phenomena for read/write operations, may lead to a novel concept for magnetic recording with high areal density.

Materials and methods: The CoPtCr films were deposited by an epitaxy-like sputtering and contained several perpendicularly magnetized granular-media layers with different coercivities; they are very much like the state-of-the-art perpendicular magnetic medium, which can be found in today's hard disc drives. Magnetoresistive properties of bulk films were assessed by measuring the film resistance in the standard Van der Pauw geometry, while the local transport was probed by the point-contact technique.

Results: The bulk measurements showed only a negligible magnetoresistance of less than 0.02%. In contrast, the local point-contact measurements revealed giant-magnetoresistance-like changes ΔR in local resistance of the contact R with more than 10,000% ratio ΔR/R.

Conclusion: The observed large and local magnetoresistive effect could be tentatively attributed to a tunnel magnetoresistance between oxide-segregated CoPtCr grains with different coercivities. The tunneling picture of electronic transport in our granular medium was confirmed by the observation of tunneling-like current-voltage characteristics of the contacts and bias dependence of the contact magnetoresistance - both the local point-contact resistance and magnetoresistance were found to decrease with the applied dc bias.

Background: We recently reported on preferential deposition of bare fluorescent diamond particles FDP-NV-700/800nm (FDP-NV) in the liver following intravenous administration to rats. The pharmacokinetics of FDP-NV in that species indicated short residency in the circulation by rapid clearance by the liver. Retention of FDP-NV in the liver was not associated with any pathology. These observations suggested that cancer therapeutics, such as doxorubicin, linked to FDP-NV, could potentially serve for anti-cancer treatment while sparing toxicities of peripheral organs.

Purpose: To generate proof-of-concept (POC) and detail mechanisms of action of doxorubicin-coated FDP-NV-700/800nm (FDP-DOX) as a prospective chemotherapeutic for metastatic liver cancer.

Methods: FDP-DOX was generated by adsorption chemistry. Experimental design included concentration and time-dependent efficacy studies as compared with naïve (baren) FDP-NV in in vitro liver cancer cells models. Uptake of FDP-NV and FDP-DOX by HepG-2, Hep-3B and hCRC organoids were demonstrated by flow-cytometry and fluorescent microscopy. FDP-DOX pharmacodynamic effects included metabolic as well as cell death biomarkers Annexin V, TUNEL and LDH leakage. DOX desorpted from FDP-DOX was assessed by confocal microscopy and chemical assay of cells fractions.

Results: FDP-DOX efficacy was dose- and time-dependent and manifested in both liver cancer cell lines and human CRC organoids. FDP-DOX was rapidly internalized into cancer cells/organoids leading to cancer growth inhibition and apoptosis. FDP-DOX disrupted cell membrane integrity as evident by LDH release and suppressing mitochondrial metabolic pathways (AlamarBlue assay). Access of free DOX to the nuclei was confirmed by direct UV-Visible fluorescent assay and confocal microscopy of DOX fluorescence.

Conclusion: The rapid uptake and profound cancer inhibition observed using FDP-DOX in clinically relevant cancer models, highlight FDP-DOX promise for cancer chemotherapeutics. We also conclude that the in vitro data justify further investment in in vivo POC studies.

Purpose: The ability of silver nanoparticles (AgNPs) of different sizes to influence copper metabolism in mice is assessed.

Materials and methods: AgNPs with diameters of 10, 20, and 75 nm were fabricated through a chemical reduction of silver nitrate and characterized by UV/Vis spectrometry, transmission and scanning electronic microscopy, and laser diffractometry. To test their bioactivity, Escherichia coli cells, cultured A549 cells, and C57Bl/6 mice were used. The antibacterial activity of AgNPs was determined by inhibition of colony-forming ability, and cytotoxicity was tested using the MTT test (viability, %). Ceruloplasmin (Cp, the major mammalian extracellular copper-containing protein) concentration and enzymatic activity were measured using gel-assay analyses and WB, respectively. In vitro binding of AgNPs with serum proteins was monitored with UV/Vis spectroscopy. Metal concentrations were measured using atomic absorption spectrometry.

Results: The smallest AgNPs displayed the largest dose- and time-dependent antibacterial activity. All nanoparticles inhibited the metabolic activity of A549 cells in accordance with dose and time, but no correlation between cytotoxicity and nanoparticle size was found. Nanosilver was not uniformly distributed through the body of mice intraperitoneally treated with low AgNP concentrations. It was predominantly accumulated in liver. There, nanosilver was included in ceruloplasmin, and Ag-ceruloplasmin with low oxidase activity level was formed. Larger nanoparticles more effectively interfered with the copper metabolism of mice. Large AgNPs quickly induced a drop of blood serum oxidase activity to practically zero, but after cancellation of AgNP treatment, the activity was rapidly restored. A major fraction of the nanosilver was excreted in the bile with Cp. Nanosilver was bound by alpha-2-macroglobulin in vitro and in vivo, but silver did not substitute for the copper atoms of Cp in vitro.

Conclusion: The data showed that even at low concentrations, AgNPs influence murine copper metabolism in size-dependent manner. This property negatively correlated with the antibacterial activity of AgNPs.