Fractal Character of Dynamic Light Scattering of Particles

Dynamic light scattering signals from particles, exhibit fractal characteristics. This feature can be used to determine the particle size. The use of the fractal dimension, as a quantitative method to analyze the properties of dynamic light scattering signals from submicron particles, is presented. The analysis is performed directly on the time‐resolved scattered intensity, and the Box Dimensions of light scattering signals of particles with diameters 100, 200, 500 and 1000 nm. The experimental results show that the fractal dimensions of light scattering signals correlate well with particle size. In the submicron size range, the smaller the particles, the larger their fractal dimensions. Compared with the PCS technique, only several hundreds of samples are required in the fractal method. Therefore, the data processing is easily accomplished. However, this method only provides the mean particle size, but not the particle size distribution.     

Efficient Cellular Internalization and Transport of Bowl-Shaped Polydopamine Particles

In drug delivery applications, particle-based systems have been used widely due to their physicochemical properties such as size, shape, and surface charge to achieve desirable properties in intracellular environments. The way in which nanoparticles enter a biological cell is an important factor in determining their efficacy as drug carriers, their biodistribution, and toxicity. Most research thus far has focused on the comparison of spherical and rod-like particles on cellular internalization and transport. Here, the synthesis of bowl-shaped polydopamine (PDA) mesoporous nanoparticles with an average diameter of 200 nm and well-controlled radially oriented mesochannels are reported. By incubating bowl-shaped PDA nanoparticles and spherical nanoparticles with HeLa cells, their internalization behaviors are investigated using a suite of characterization techniques. Extensive experimental results demonstrate that bowl-shaped PDA nanoparticles adhere to the cell more efficiently and a faster rate of cellular uptake of bowl-shaped nanoparticles compared to their spherical counterparts. Overall, the cellular internalization behavior of particles is shape-dependent, and such information is crucial in designing nanoparticles for biomedical applications.     

Internalisation of engineered nanoparticles into mammalian cells in vitro: influence of cell type and particle properties

Cellular internalisation of industrial engineered nanoparticles is undesired and a reason for concern. Here we investigated and compared the ability of seven different mammalian cell cultures in vitro to incorporate six kinds of engineered nanoparticles, focussing on the role of cell type and particle properties in particle uptake. Uptake was examined using light and electron microscopy coupled with energy dispersive X-ray spectroscopy (EDX) for particle element identification. Flow cytometry was applied for semi-quantitative analyses of particle uptake and for exploring the influence on uptake by the phagocytosis inhibitor Cytochalasin D (CytoD). All particles studied were found to enter each kind of cultured cells. Yet, particles were never found within cell nuclei. The presence of the respective particles within the cells was confirmed by EDX. Live-cell imaging revealed the time-dependent process of internalisation of technical nanoparticles, which was exemplified by tungsten carbide particle uptake into the human skin cells, HaCaT. Particles were found to co-localise with lysosomal structures within the cells. The incorporated nanoparticles changed the cellular granularity, as measured by flow cytometry, already after 3 h of exposure in a particle specific manner. By correlating particle properties with flow cytometry data, only the primary particle size was found to be a weakly influential property for particle uptake. CytoD, an inhibitor of actin filaments and therewith of phagocytosis, significantly inhibited the internalisation of particle uptake in only two of the seven investigated cell cultures. Our study, therefore, supports the notion that nanoparticles can enter mammalian cells quickly and easily, irrespective of the phagocytic ability of the cells.     

Influence of the Morphology of Lysozyme‐Shelled Microparticles on the Cellular Association,Uptake, and Degradation in Human Breast Adenocarcinoma Cells

The ultrasound‐assisted self‐assembly and cross‐linking of lysozyme at the water–air and water–perfluorohexane interfaces are shown to produce lysozyme‐shelled hollow microbubbles (LSMBs) and microcapsules (LSMC), respectively. The arrangement of lysozyme at the air–liquid or oil–liquid interfaces is accompanied by changes in the bioactivity and conformational state of the protein. The interaction of LSMB and LSMC with human breast adenocarcinoma cells (SKBR3) is studied. LSMB and LSMC are phagocyted by cells within 2 h without exerting a cytotoxic activity. The cellular internalization kinetics of LSMB and LSMC and the effects on cell cycle are evaluated using flow cytometry. Evidence for the internalization of microparticles and degradation within the cell are also monitored by confocal and scanning electron microscopic analyses. The integrity of cell membrane and cell cycle is not affected by LSMBs and LSMCs uptake. These studies show that the positively charged LSMB and LSMC are not cytotoxic and can be readily internalized and degraded by the SKBR3 cells. LSMBs and LSMCs show a different uptake kinetics and intracellular degradation pattern due to differences in the arrangement of the protein at the air–liquid or oil–liquid interfaces.     

Probing Chemical and Mechanical Nanodomains in Copolymer Nanorods with Correlative Atomic Force Microscopy—Nano‐correscopy

The interplay between size, shape, mechanical properties, and surface chemistry of nanoparticles orchestrates cellular internalization, toxicity, circulation time, and biodistribution. Therefore, the safety of nanoparticles hinges on our ability to quantify nanoscale physicochemical characteristics. Current characterization tools, due to their limited resolution, are unable to map these properties correlatively at nanoscale. An innovative use of atomic force microscopy‐based techniques, namely nano‐correscopy, overcomes this limitation and offers multiprobe capability to map mechanical (viscous and elastic) and chemical domains of nanoparticles correlatively. The strengths of this approach are demonstrated using polymer composite nanorods: m‐PEG‐PLGA ((m‐PEG–methoxy‐poly (ethylene glycol)‐b‐poly (lactic‐co‐glycolic) acid). Precise distribution of PLGA (monomers of lactide and glycolide) and poly(ethylene glycol) (PEG) polymer across nanorods is identified. The hydrophobic lactide component is found predominantly at the apex, while hydrophilic glycolide and PEG assembled at the body of the nanorods and correlate with a gradient of nanomechanical properties. New knowledge of how both nanochemical domains and nanomechanical properties are distributed across the nanorod will allow elucidating the interactions of nanorods with the proteins and biomolecules in the future, which will directly influence the fate of nanorods in vivo and will guide new synthesis methods.     

Relationship between size and surface modification of silica particles and enhancement and suppression of inflammatory cytokine production by lipopolysaccharide- or peptidoglycan-stimulated RAW264.7 macrophages

Although nanomaterials are used in an increasing number of commodities, the relationships between their immunotoxicity and physicochemical properties such as size or surface characteristics are not fully understood. Here we demonstrated that pretreatment with amorphous silica particles (SPs) of various sizes (diameters of 10–1000 nm), with or without amine surface modification, significantly decreased interleukin 6 production by RAW264.7 macrophages following lipopolysaccharide or peptidoglycan stimulation. Furthermore, nanosized, but not microsized, SPs significantly enhanced tumor necrosis factor-α production in macrophages stimulated with lipopolysaccharide. This altered cytokine response was distinct from the inflammatory responses induced by treatment with the SPs alone. Additionally, the uptake of SPs into macrophages by phagocytosis was found to be crucial for the suppression of macrophage immune response to occur, irrespective of particle size or surface modification. Together, these results suggest that SPs may not only increase susceptibility to microbial infection, but that they may also be potentially effective immunosuppressants.     

Optical formation and manipulation of particle and cell patterns using a tapered optical fiber

A method for optical formation and controllable manipulation of particle and cell patterns using a tapered optical fiber is demonstrated. With a laser beam at 980‐nm wavelength launched into the fiber, different sized silica particles were formed into particle patterns (both one‐dimensional chains and two‐dimensional arrays) with different particle numbers by optical binding. The formed particle patterns can be controllably manipulated in three dimensions. Using yeast cells as an example, it was demonstrated that the method is applicable for the formation of biological cell patterns, without damage to the yeast cell viability. This method provides a new facile way for biophotonic and biological researches with particles and cells in a highly organized manner.     

Monosaccharide-Directed Selective Internalization of Gold and Silver Nanoparticles in Hepatic Cancer Cells

The therapeutic success of nanomedicines requires nanomaterials to either adhere to the surface or internalize within the cytoplasm. The endocytosis phenomenon is controlled by the nanomaterial's shape, size, composition, charge, and capping molecules. The membrane potential-based non-specific internalization of therapeutic nanomedicines offers limited benefits than receptor-based specific delivery. Glut receptor-based internalization of glucose molecules is a well-known process in cancerous cells, which is one of the most exploited strategies to target cancer cells using nanoparticles. However, the internalization process of other structurally similar monosaccharides (D-Galactose, Mannose, and D-Fructose) conjugated nanoparticles remains to be unexplored. Herein, D-Glucose, D-Galactose, Mannose, and D-Fructose-coated AuNPs and AgNPs have been synthesized and studied the role of Glut receptors in their internalization in liver cancer cells, and compared them with non-cancerous cells. Results revealed that almost all monosaccharide-coated NPs exhibited high uptake in liver cancer cells than non-cancerous cells. Glut-1 receptor is observed to play a key role in the uptake and inhibition of Glut-1 receptors by genistein lead to a significant decrease in nanoparticle uptake. In conclusion, monosaccharide-conjugated nanoparticles can be used to direct the selective internalization of AuNPs and AgNPs in hepatic cancer cells to realize therapeutic and imaging applications.     

Effect of serum proteins on polystyrene nanoparticle uptake and intracellular trafficking in endothelial cells

The physico-chemical properties of nanoparticles (NPs), such as small dimensions, surface charge and surface functionalization, control their capability to interact with cells and, in particular, with sub-cellular components. This interaction can be also influenced by the adsorption of molecules present in biological fluids, like blood, on NP surface. Here, we analysed the effect of serum proteins on 49 and 100 nm red fluorescent polystyrene NP uptake in porcine aortic endothelial (PAE) cells, as a model for vascular transport. To this aim, NP uptake kinetic, endocytic pathway and intracellular trafficking were studied by monitoring NPs inside cells through confocal microscopy and multiple particle tracking (MPT). We demonstrated that NPs are rapidly internalized by cells in serum-free (SF) medium, according to a saturation kinetic. Conversely, in 10% foetal bovine serum-enriched (SE) medium, NP uptake rate results drastically reduced. Moreover, NP internalization depends on an active endocytic mechanism that does not involve clathrin- and caveolae-mediated vesicular transport, in both SE and SF media. Furthermore, MPT data indicate that NP intracellular trafficking is unaffected by protein presence. Indeed, approximately 50–60% of internalized NPs is characterized by a sub-diffusive behaviour, whereas the remaining fraction shows an active motion. These findings demonstrate that the unspecific protein adsorption on NP surface can affect cellular uptake in terms of internalization kinetics, but it is not effective in controlling active and cellular-mediated uptake mechanisms of NPs and their intracellular routes.     

Correlation between structure and optoelectronic properties in a two‐dimensional nanoparticle assembly

The optical properties of two‐dimensional assemblies of metal nanoparticles are strongly influenced by the morphological configuration of the metal particles in the layer. Therefore, we correlate the structural and optical properties of two‐dimensional, hexagonal gold nanoparticle arrays. We characterize the structure of the arrays using grazing‐incidence small angle X‐ray scattering (GISAXS). From the GISAXS pattern, we determine the size of the gold particles as well as the lattice spacing of the hexagonal assembly. Based upon these parameters we calculate the dielectric function of the gold particle array using the Maxwell–Garnett effective medium theory. We further deduce the absorption spectrum which closely follows the measured absorption and photoconductance spectrum. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Improved control of the phosphorous surface concentration during in‐line diffusion of c‐Si solar cells by APCVD

Emitter formation for industrial crystalline silicon (c‐Si) solar cells is demonstrated by the deposition of phosphorous‐doped silicate glasses (PSG) on p‐type monocrystalline silicon wafers via in‐line atmospheric pressure chemical vapor deposition (APCVD) and subsequent thermal diffusion. Processed wafers with and without the PSG layers have been analysed by SIMS measurements to investigate the depth profiles of the resultant phosphorous emitters. Subsequently, complete solar cells were fabricated using the phosphorous emitters formed by doped silicate glasses to determine the impact of this high‐throughput doping method on cell performance. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Preparation and performance of the polyethylene-supported polyvinylidene fluoride/cellulose acetate butyrate/nano-SiO<Subscript>2</Subscript> particles blended gel polymer electrolyte

The preparation of polyethylene-supported poly(vinylidene fluoride)/cellulose acetate butyrate/nano-SiO₂ particle (PVDF-CAB-SiO₂/PE) blended gel polymer electrolytes (GPEs) is reported here. The electrolyte uptake, mechanical properties, thermal stability, and electrochemical performance of these electrolytes are characterized to evaluate their potential application in lithium-ion batteries (LIBs). The results indicate that the particle size of SiO₂ can be adjusted by the tetraethyl orthosilicate (TEOS) concentration and affects the physicochemical properties of the membrane. By doping 5 wt.% SiO₂ (500 nm) into the PVdF-CAB blended polymer, the porosity of the membrane increases from 40 to 42.3 %, the mechanical strength from 117.3 to 138.7 MPa, the electrolyte uptake from 149 to 195 %, the oxidation decomposition potential from 4.7 to 5.2 V, and the ionic conductivity of the corresponding GPE is improved from 1.16 to 2.98 mS cm^?1 at ambient temperature. The PVDF-CAB-SiO₂/PE-based GPE and the two electrodes are suitably compatible, and the thermal stability is higher than that of the polyethylene (PE) membrane. The LIBs with the as-prepared GPE also exhibit enhanced discharge capacity and cycle stability, indicating the promising application of these GPEs in LIBs.     

In Vitro Evaluation of Non‐Protein Adsorbing Breast Cancer Theranostics Based on 19F‐Polymer Containing Nanoparticles

Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self‐assembly of either linear or star‐shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non‐toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX‐NPs into breast cancer cells, and in vitro ¹⁹F‐MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for ¹⁹F‐MRI.     

Chip‐Free Microscale‐Incubator‐Based Synthesis of Chitosan‐Based Gene Silencing Nanoparticles

The development of polymer‐based nanoparticles to ferry siRNA continues to evolve. It is becoming increasingly apparent that gene silencing nanoparticles produced by conventional bulk manufacturing techniques often exhibit physicochemical heterogeneity within and between batches that can affect the biological performance. Here a new facile and robust “chip‐free” method is presented, termed chip‐free agitation‐generated droplets (CAD) preparation, using chitosan‐based gene silencing nanoparticles as an example. The CAD‐prepared silencing particles, in comparison to the particles prepared by the conventional bulk protocol, exhibit lower surface charge (9 mV vs 21 mV at N/P = 5), higher stability (≈40% higher binding affinity and up to 30% less morphological deformation), and are less prone to aggregation measured by nanoparticle tracking analysis over a period of one month. Furthermore, these physical attributes contribute up to 19% higher in cell viability at N/P = 5, while the gene silencing of enhanced green fluorescent protein remains constant in a human cell line. Control of particle properties is necessary to advance siRNA‐based delivery; the CAD preparation represents a physical complement to chemical design modifications, which can be readily transferred among research labs and utilized for alternative polymer systems.     

Real‐Time Detection of Nanoparticles Interaction with Lipid Membranes Using an Integrated Acoustical and Electrical Multimode Biosensor

Understanding interactions of nanoparticles with biomembranes is critical in nanomedicine and nanobiotechnology. The underlying mechanisms still remain unclear due to the fact that there are no reliable tools to follow such complex processes. In this work, the interactions between gold nanoparticles (AuNPs) and the supported lipid bilayer (SLB) are monitored in situ by a multimode biosensor integrating a quartz crystal microbalance with dissipation function (QCM‐D) and a field effect transistor (FET). Real‐time responses of frequency shift (Δf), dissipation (ΔD), and ion current (ΔI) are simultaneously recorded to provide complementary information for AuNPs translocation across the SLB. The combined mass loading, mechanical and electrical measurements reveal the dynamics of the particle–membrane interactions as well as the formation of transient pores or permanent defects in the membrane. AuNPs with different diameters, surface charge, and ligand properties are used to study their translocation behaviors, including adsorption on or desorption from the membrane surface, diffusion into or penetration through the lipid bilayer. This multimode sensing approach provides insights into the mechanism of the particle–membrane interactions and suggests a method of label‐free screening of nanomaterials' interaction with model membranes in a real‐time manner.     

Recent Advances in the Synthesis and Applications of Ultrasmall Bimetallic Nanoclusters

Ultrasmall bimetallic nanoclusters (or bi‐MNCs for short) have recently emerged as a new class of multi‐functional nanoparticles due to their ultrasmall size (typically below 2 nm), unique molecular‐like properties (e.g., quantized charging and strong luminescence), controlled cluster compositions (at the atomic level), synergistic physicochemical properties, and rich surface chemistry. Such intriguing properties have motivated the cluster community to develop efficient methods for the synthesis of high‐quality bi‐MNCs, which can also be seen from the quantum increase of reported synthetic protocols for bi‐MNCs. Recent advances in the development of efficient synthesis methods for high‐quality bi‐MNCs also facilitate the application explorations of bi‐MNCs in diverse fields like catalysis, sensors, and biomedicine. This Review article first surveys current progress in the synthesis of bi‐MNCs, especially for those NCs with good control of cluster size and composition, followed by a detailed discussion on some unique physicochemical properties of bi‐MNCs. The intriguing properties of bi‐MNCs have made them ideal platforms for application explorations in catalysis, sensors, and biomedicine, which are discussed in the second section. In the last section, a brief outlook on future developments of functional bi‐MNCs is presented, with a particular focus on the controlled synthesis and practical applications of bi‐MNCs.     

Liposomal Templating,Association with Mammalian Cells,and Cytotoxicity of Poly(vinyl alcohol) Physical Hydrogel Nanoparticles

The assembly, cellular internalization, and cytotoxicity of nanoparticles based on physical hydrogels of poly(vinyl alcohol) (PVA) are reported. PVA nanoparticles are assembled using a liposomal templating technique followed by removal of the lipids using isopropanol, a process that requires the presence of a custom‐made block copolymer, poly(vinyl alcohol‐b‐vinyl pyrrolidone), to avoid aggregation of the nanoparticles. Polymer hydrogelation is induced via incubation in aqueous isopropyl alcohol solution, which results in PVA hydrogel nanoparticles (PVA HNP) with excellent colloidal stability and stability towards disintegration over at least 24 h. Pristine PVA HNP are found to be remarkably stealth‐like and exhibit negligible cellular internalization. This feature is likely inherent with the low fouling nature of PVA and makes PVA HNP attractive for targeted drug delivery with a low level of association with non‐targeted cells and tissues. Blending PVA with varied amounts of collagen results in colloidal hydrogel particles with a well pronounced tendency towards association with mammalian cells, specifically hepatocytes and endothelial cells. The association of PVA HNP elicits minimal changes in cellular proliferation, making these novel hydrogel particles convenient tools for drug delivery applications and creation of implantable artificial organelles and sensors.     

Transient Response of Particle Distribution in a Chamber to Transient Particle Injection

We inject a large number of newly created nano‐particle aggregates into a chamber for the purpose of removing harmful contents in an indoor environment. This study is to experimentally and numerically investigate transient response of particle distributions to particle injections. A room‐sized chamber of 4 m × 2.1 m × 2.4 m is connected to a specially designed particle‐injection system, with two Optical Particle Counters used to simultaneously measure particle‐number densities with the size range from 0.3 μm to 10 μm at the inlet and in the chamber. A velocity probe measures the flow that is up to 1 m/s. An Euler‐type particulate‐phase‐transport model is developed and validated by comparing with experimental data. The study shows that the transient behavior of particle distributions is determined by many factors, including particle size, particle settling speed, sampling location, and velocity distribution. Particle number densities decrease in time more quickly for large particles than for small particles, and locations farther downstream in the chamber correlate more weakly with the inlet injection.     

Structure activity relationship of magnetic particles as MR contrast agents

Structure activity relationship (SAR) of superparamagnetic MR contrast agents is discussed based on physicochemical properties and relaxivity data of 16 different particles. All the magnetic particles reduce both relaxation times, T1 and T2. The effect on T2 is stronger than the effect on T1. The relaxation efficacy varies over a wide range. Minor modifications in the preparation of the magnetic particles result in products with different susceptibility properties. The T2 relaxivity is dependent upon the magnetic susceptibility as well as particle size. Small particles reduce the relaxation times to a larger extent than the larger particles. No significant difference in relaxivity is observed between compact and porous particles. Magnetic particles coated with nonmagnet polymer are effective relaxation agents, while nonmagnetic monodisperse particles show no effect on the relaxivity.     

Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells

The cytotoxic effects of silica nanoparticles (SNPs) on different human cancer cells, as well as the uptake kinetics and pathways of SNPs have been studied here. SNPs with the diameter of ≈20 nm induced a dose‐dependent cytotoxicity in both gastric cancer cells (MGC80–3) and cervical adenocarcinoma epithelial cells (HeLa), but MGC80–3 cells were more susceptible to the cytotoxic effect induced by SNPs. Changes in the nuclear morphology and flow cytometric analysis with annexin V/PI double staining show that SNPs induced a higher degree of apoptosis in MGC80–3 cells. Accordingly, more remarkable reactive oxygen species (ROS) burst is detected in SNP‐treated MGC80–3 cells. Using fluorescein isothiocyanate (FITC)‐labeled SNPs and flow cytometry, it is found that the uptake of SNPs is more efficient in MGC80–3 than in HeLa cells. SNPs are internalized into both cancer cells through energy‐dependent pathway. Inhibitor studies with dynasore and methyl‐β‐cyclodextrin show that these cancer cells took up 20 nm SNPs mainly through the caveolin‐mediated endocytosis, while in HeLa cells SNPs internalization was also via dynamin‐dependent clathrin‐mediated pathway. These findings indicate that SNPs cause differential cytotoxic effects in different human cancer cells, which might be related to the uptake process and efficiency toward these cancer cells.