Nanotechnology, Science and Applications最新文献

Background: The limitations of optical microscopy to determine the cellular localization of label-free nanoparticles prevent a solid prediction of the cellular effect of particles intended for medical applications. To avoid the strong physicochemical changes associated with fluorescent labelling, which often result in differences in cellular uptake, efficiency and toxicity of particles, novel detection techniques are required.

Methods: In the present study, we determined the intracellular content of unlabeled SPIONs by analyzing refractive index (RI)-based images from holotomographic three-dimensional (3D) microscopy and side scatter data measured by flow cytometry. The results were compared with the actual cellular SPION amount as quantified by atomic emission spectroscopy (AES).

Results: Live cell imaging by 3D holotomographic microscopy demonstrated cell-specific differences in intracellular nanoparticle uptake in different pancreatic cell lines. Thus, treatment of PANC-1^{SMAD4 (1-4)} and PANC-1^{SMAD4 (2-6)} with SPIONs resulted in a significant increase in number of areas with higher RI, whereas in PANC-1, SUIT-2 and PaCa DD183, only a minimal increase of spots with high RI was observed. The increase in areas with high RI was in accordance with the SPION content determined by quantitative iron measurements using AES. In contrast, determination of the SPION amount by flow cytometry was strongly cell type-dependent and did not allow the discrimination between intracellular and membrane-bound SPIONs. However, flow cytometry is a very rapid and reliable method to assess the cellular toxicity and allows an estimation of the cell-associated SPION content.

Conclusion: Holotomographic 3D microscopy is a useful method to distinguish between intracellular and membrane-associated particles. Thus, it provides a valuable tool for scientists to evaluate the cellular localization and the particle load, which facilitates prediction of potential toxicity and efficiency of nanoparticles for medical applications.

Background: Recently, we reported the safety and biocompatibility of fluorescent diamond particles, FDP-NV-Z-800nm (FDP-NV) injected intravenously into rats, where no morbidity and mortality were noted over a period of 3 months. The acute effects of FDP-NV-800nm particles on cultured human endothelial and hepatic cells remain unexplored.

Purpose: In this study, we aimed to explore select cellular and biochemical functions in cultured human umbilical endothelial cells (HUVEC) and a human hepatic cancer cell line (HepG-2) exposed to FDP-NV-800 in vitro at exposure levels within the pharmacokinetics (Cmax and the nadir) previously reported in vivo.

Methods: Diverse cellular and biochemical functions were monitored, which cumulatively can provide insights into some vital cellular functions. Cell proliferation and migration were assessed by quantitative microscopy. Mitochondrial metabolic functions were tested by the MTT assay, and cytosolic esterase activity was studied by the calcein AM assay. Chaperons (CHOP), BiP and apoptosis (caspase-3 activation) were monitored by using Western blot (WB). MAPK Erk1/2 signaling was assessed by the detection of the phosphorylated form of the protein (P-Erk 1/2) and its translocation into the cell nucleus.

Results: At all concentrations tested (0.001-0.1mg/mL), FDP-NV did not affect any of the biomarkers of cell integrity of HepG2 cells. In contrast, the proliferation of HUVEC was affected at the highest concentration tested (0.1mg/mL, C_max). Exposure of HUVEC to (0.01 mg/mL) FDP-NV had a mild-moderate effect on cell proliferation as evident in the MTT assay and was absent when proliferation was assessed by direct cell counting or by using the calcein AM assays. In both cell types, exposure to the highest concentration (0.1 mg/mL) of FDP-NV did neither affect FBS-stimulated cell signaling (MAPK Erk1/2 phosphorylation) nor did it activate of Caspase 3.

Conclusion: Our data suggest that FDP-NV-800nm are largely biocompatible with HepG-2 cells proliferation within the pharmacokinetic data reported previously. In contrast, HUVEC proliferation at the highest exposure dose (0.1 mg/mL) responded adversely with respect to several biomarkers of cell integrity. However, since the C_max levels are very short-living, the risk for endothelial injury is likely minimal for slow rate cell proliferation such as endothelial cells.

Introduction: Biological research relies on the culture of mammalian cells, which are prone to changes in phenotype during experiments involving several passages of cells. In regenerative medicine, specifically, there is an increasing need to expand the characterisation landscape for stem cells by identifying novel stable markers. This paper reports on a novel electric cell-substrate impedance sensing-based electroanalytical diagram which can be used for the "electrical characterisation" of cell monolayers consisting of smooth muscle cells, endothelial cells or co-culture.

Materials and methods: Interdigitated electrodes were microfabricated using standard cleanroom procedures and integrated into cell chambers. Electrochemical impedance spectroscopy data were acquired for 2 vascular cell types after they formed monolayers on the electrodes.

Results and discussion: A Mean impedance per unit area vs Mean phase plots provided a reproducible, visually obvious and statistically significant method of characterising cell monolayers. This electroanalytic diagram has never been used in previous papers, but it confirms findings by other research groups using similar approaches that the complex impedance spectra of different cell type are different. Further work is required to determine whether this method could be extended to other cell types, and if this is the case, a library of "signature spectra" could be generated for "electrical characterisation" of cells.

Purpose: Metal-based nanoparticles (M-NPs) have attracted great attention in nanomedicine due to their capacity to amplify and improve the tumor targeting of medical beams. However, their simple, efficient, high-yield and reproducible production remains a challenge. Currently, M-NPs are mainly synthesized by chemical methods or radiolysis using toxic reactants. The waste of time, loss of material and potential environmental hazards are major limitations.

Materials and methods: This work proposes a simple, fast and green strategy to synthesize small, non-toxic and stable NPs in water with a 100% production rate. Ionizing radiation is used to simultaneously synthesize and sterilize the containing NPs solutions. The synthesis of platinum nanoparticles (Pt NPs) coated with biocompatible poly(ethylene glycol) ligands (PEG) is presented as proof of concept. The physicochemical properties of NPs were studied by complementary specialized techniques. Their toxicity and radio-enhancing properties were evaluated in a cancerous in vitro model. Using plasmid nanoprobes, we investigated the elementary mechanisms underpinning radio-enhancement.

Results and discussion: Pt NPs showed nearly spherical-like shapes and an average hydrodynamic diameter of 9 nm. NPs are zero-valent platinum successfully coated with PEG. They were found non-toxic and have the singular property of amplifying cell killing induced by γ-rays (14%) and even more, the effects of carbon ions (44%) used in particle therapy. They induce nanosized-molecular damage, which is a major finding to potentially implement this protocol in treatment planning simulations.

Conclusion: This new eco-friendly, fast and simple proposed method opens a new era of engineering water-soluble biocompatible NPs and boosts the development of NP-aided radiation therapies.

Recently, suspensions of several nanoparticles or nanocomposites have attained a vast field of application in biomedical research works in some specified conditions and clinical trials. These valuable suspensions, which allow the nanoparticles to disperse and act in homogenous and stable media, are named as nanofluids. Several studies have introduced the advantages of nanofluids in biomedical approaches in different fields. Few review articles have been reported for presenting an overview of the wide biomedical applications of nanofluids, such as diagnosis and therapy. The review is focused on nanosuspensions, as the nanofluids with solid particles. Major applications are focused on nanosuspension, which is the main type of nanofluids. So, concise content about major biomedical applications of nanofluids in drug delivery systems, imaging, and antibacterial activities is presented in this paper. For example, applying magnetic nanofluid systems is an important route for targeted drug delivery, hyperthermia, and differential diagnosis. Also, nanofluids could be used as a potential antibacterial agent to overcome antibiotic resistance. This study could be useful for presenting the novel and applicable methods for success in current medical practice.

Purpose: Cordycepin, a natural product isolated from the fungus Cordyceps militaris, is a potential candidate for breast cancer therapy. However, due to its structural similarity with adenosine, cordycepin is rapidly metabolized into an inactive form in the body, hindering its development as a therapeutic agent. In the present study, we have prepared cordycepin as nanoparticles in poly(lactic-co-glycolic acid) (PLGA) and compared their cellular uptake, cytotoxicity and hemolytic potential with free cordycepin.

Materials and methods: Cordycepin-loaded PLGA nanoparticles (CPNPs) were prepared by the double-emulsion solvent evaporation method. Physico-chemical characterization of the nanoparticles was done by zetasizer, transmission electron microscopy (TEM) and reverse-phase high-pressure liquid chromatography (RP-HPLC) analyses. Cellular uptake and cytotoxicity of CPNPs and free drug were tested in human breast cancer cells (MCF7). Hemolytic potential of both of these forms was evaluated in rat red blood cells (RBCs).

Results: Physico-chemical characterization revealed that CPNPs were spherical in shape, possessed a size range of 179-246 nm, and released the encapsulated drug sustainably over a period of 10 days. CPNPs exhibited a high level of cellular uptake and cytotoxicity than the free drug in MCF-7 cells. While CPNPs were not toxic to rat RBCs even at high concentrations, free cordycepin induced hemolysis of these cells at relatively low concentration.

Conclusion: Our results reveal that delivery as CPNPs could enhance the clinical efficacy of cordycepin substantially.

α-Mangostin, a xanthone derivative from the pericarp of Garcinia mangostana L., has numerous bioactivities and pharmacological properties. However, α-mangostin has low aqueous solubility and poor target selectivity in the human body. Recently, nanoparticle drug delivery systems have become an excellent technique to improve the physicochemical properties and effectiveness of drugs. Therefore, many efforts have been made to overcome the limitations of α-mangostin through nanoparticle formulations. Our review aimed to summarise and discuss the nanoparticle drug delivery systems for α-mangostin from published papers recorded in Scopus, PubMed and Google Scholar. We examined various types of nanoparticles for α-mangostin to enhance water solubility, provide controlled release and create targeted delivery systems. These forms include polymeric nanoparticles, nanomicelles, liposomes, solid lipid nanoparticles, nanofibers and nanoemulsions. Notably, nanomicelle modification increased α-mangostin solubility increased more than 10,000 fold. Additionally, polymeric nanoparticles provided targeted delivery and significantly enhanced the biodistribution of α-mangostin into specific organs. In conclusion, the nanoparticle drug delivery system could be a promising technique to increase the solubility, selectivity and efficacy of α-mangostin as a new drug candidate in clinical therapy.

Introduction: In this work we selected components, developed technology and studied a number of parameters of polymer nanocomposite materials, remembering that the material would have high optical and good mechanical characteristics, good sorption ability in order to ensure high value of the optical signal for a short time while maintaining the initial geometric shape. In addition, if this nanocomposite is used for medicine and biology (biocompatible or biocidal materials or the creation of a sensor based on it), the material must be non-toxic and/or biocompatible. We study the creation of polymer nanocomposites which may be applied as biocompatible materials with new functional parameters.

Material and methods: A number of polymer nanocomposites based on various urethane-acrylate monomers and nanoparticles of gold, silicon oxides, zinc and/or titanium oxides are obtained, their mechanical (microhardness) properties and wettability (contact angle) are studied. The set of required, biology-related properties of these materials, such as toxicity and sorption of microorganisms are also investigated in order to prove their possible applicability.

Results and discussion: The composition of the samples influences their microhardness and the value of contact angle, which means that varying with the monomer and the metallic, oxide nanoparticles composition, we could change these parameters. Besides it, the set of required, biology-related properties of these materials, such as toxicity and sorption of microorganisms were also investigated in order to prove their possible applicability. It was shown that the materials are non-toxic, the adhesion of microorganisms on their surface also could be varied by changing their composition.

Conclusion: The presented polymer nanocomposites with different compositions of monomer and the presence of nanoparticles in them are prospective material for a possible bio-application as it is biocompatible, not toxic. The sorption of microorganism could be varied depending on the type of bacterias, the monomer composition, and nanoparticles.

Introduction: Recent formulation and microencapsulation studies of probucol (PB) using the polymer sodium alginate (SA) and bile acids have shown promising results but PB stability, and pharmacology profiles remain suboptimal. This study aimed to investigate novel polymers for the nano and micro encapsulation of PB, with the anti-inflammatory bile acid ursodeoxycholic acid (UDCA).

Material and methods: Six formulations using three types of polymers were investigated with and without UDCA. The polymers were NM30D, RL30D, and RS30D and they were mixed with SA and PB at set ratios and microencapsulated using oscillating-voltage-mediated nozzle technology coupled with ionic gelation. The microcapsules were examined for physical and biological effects using pancreatic β-cells.

Results and discussion: UDCA addition did not adversely affect the morphology and physical features of the microcapsules. Despite thermal stability remaining unchanged, bile acid incorporation did enhance the electrokinetic stability of the formulation system for NM30D and RL30D polymers. Mechanical stability remained similar in all groups. Enhanced uptake of PB from the microcapsule by pancreatic β-cells was only seen with NM30D-UDCA-intercalated microcapsules and this effect was sustained at both glucose levels of 5.5 and 35.5 mM.

Conclusion: UDCA addition enhanced PB delivery and biological effects in a formulation-dependent manner.