Influence of Polymer Concentration on Drying of SPION Dispersions by Electrospinning.

To improve the physical stability of nanoparticle dispersions, several methods for their transformation into stable and easily dispersible dry products have been investigated thus far. Recently, electrospinning was shown to be a novel nanoparticle dispersion drying method, which addresses the crucial challenges of the current drying methods. It is a relatively simple method, but it is affected by various ambient, process, and dispersion parameters, which impact the properties of the electrospun product. The aim of this study was, thus, to investigate the influence of the most important dispersion parameter, namely the total polymer concentration, on the drying method efficiency and the properties of the electrospun product. The formulation was based on a mixture of hydrophilic polymers poloxamer 188 and polyethylene oxide in the weight ratio of 1:1, which is acceptable for potential parenteral application. We showed that the total polymer concentration of prior-drying samples is closely related to their viscosity and conductivity, also affecting the morphology of the electrospun product. However, the change in morphology of the electrospun product does not affect the efficiency of SPION reconstitution from the electrospun product. Regardless of the morphology, the electrospun product is not in powder form and is therefore safer to handle compared to powder nanoformulations. The optimal total polymer concentration in the prior-drying SPION dispersion, which enables the formation of an easily dispersible electrospun product with high SPION-loading (65% (w/w)) and fibrillar morphology, was shown to be 4.2% (w/v).

The shape anisotropy of magnetic nanoparticles: an approach to cell-type selective and enhanced internalization.

The effects of the shape anisotropy of nanoparticles on cellular uptake is still poorly understood due to challenges in the synthesis of anisotropic magnetic nanoparticles of the same composition. Here, we design and synthesize spherical magnetic nanoparticles and their anisotropic assemblies, namely magnetic nanochains (length ∼800 nm). Then, nanoparticle shape anisotropy is investigated on urothelial cells in vitro. Although both shapes of nanomaterials reveal biocompatibility, we havefound significant differences in the extent of their intracellular accumulation. Contrary to spherical particles, anisotropic nanochains preferentially accumulate in cancer cells as confirmed by inductively coupled plasma (ICP) analysis, indicating that control of the nanoparticle shape geometry governs cell-type-selective intracellular uptake and accumulation.

Silica Coated Bi2Se3 Topological Insulator Nanoparticles: An Alternative Route to Retain Their Optical Properties and Make Them Biocompatible.

Localized surface plasmon resonance (LSPR) is the cause of the photo-thermal effect observed in topological insulator (TI) bismuth selenide (Bi2Se3) nanoparticles. These plasmonic properties, which are thought to be caused by its particular topological surface state (TSS), make the material interesting for application in the field of medical diagnosis and therapy. However, to be applied, the nanoparticles have to be coated with a protective surface layer, which prevents agglomeration and dissolution in the physiological medium. In this work, we investigated the possibility of using silica as a biocompatible coating for Bi2Se3 nanoparticles, instead of the commonly used ethylene-glycol, which, as is presented in this work, is not biocompatible and alters/masks the optical properties of TI. We successfully prepared Bi2Se3 nanoparticles coated with different silica layer thicknesses. Such nanoparticles, except those with a thick, ≈200 nm silica layer, retained their optical properties. Compared to ethylene-glycol coated nanoparticles, these silica coated nanoparticles displayed an improved photo-thermal conversion, which increased with the increasing thickness of the silica layer. To reach the desired temperatures, a 10-100 times lower concentration of photo-thermal nanoparticles was needed. In vitro experiments on erythrocytes and HeLa cells showed that, unlike ethylene glycol coated nanoparticles, silica coated nanoparticles are biocompatible.

Electrospinning as a method for preparation of redispersible dry product with high content of magnetic nanoparticles.

One of the key technological challenges in the development of iron-oxide-based magnetic nanoparticles (MNPs) is their long-term physical stability in colloidal dispersions. This can be improved by their transformation into a dry form. Here, we introduce electrospinning as a drying method for ethanol-based and water-based MNP dispersions, which enables the preparation of high-loaded dry MNP products. The obtained easily dispersible electrospun product contained up to 50 % (w/w) of MNPs, homogeneously distributed in the fibrillar structure, which is much more compared to the products of currently available methods for drying MNP dispersions. The polymers used as building blocks of nanofibers, namely poloxamer 188 and polyethylene oxide, improved the tolerance of MNPs to high ionic strength dispersion medium and thus enhanced the short-term physical stability of MNP dispersions after reconstitution. The dry product was stable for up to 1 month at room temperature and relative humidity up to 70 %. It was in the form of a nanofiber mat, which prevented the aerosolization of MNPs and their unintentional ambient exposure. Therefore, the electrospun product with MNPs is expected to be a safer dry formulation of MNPs than the nanoparticulate powders, which are usually the final products of the conventional drying methods.

Oleic Acid Protects Endothelial Cells from Silica-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs)-Induced Oxidative Stress and Cell Death.

Superparamagnetic iron oxide nanoparticles (SPIONs) have great potential for use in medicine, but they may cause side effects due to oxidative stress. In our study, we investigated the effects of silica-coated SPIONs on endothelial cells and whether oleic acid (OA) can protect the cells from their harmful effects. We used viability assays, flow cytometry, infrared spectroscopy, fluorescence microscopy, and transmission electron microscopy. Our results show that silica-coated SPIONs are internalized by endothelial cells, where they increase the amount of reactive oxygen species (ROS) and cause cell death. Exposure to silica-coated SPIONs induced accumulation of lipid droplets (LD) that was not dependent on diacylglycerol acyltransferase (DGAT)-mediated LD biogenesis, suggesting that silica-coated SPIONs suppress LD degradation. Addition of exogenous OA promoted LD biogenesis and reduced SPION-dependent increases in oxidative stress and cell death. However, exogenous OA protected cells from SPION-induced cell damage even in the presence of DGAT inhibitors, implying that LDs are not required for the protective effect of exogenous OA. The molecular phenotype of the cells determined by Fourier transform infrared spectroscopy confirmed the destructive effect of silica-coated SPIONs and the ameliorative role of OA in the case of oxidative stress. Thus, exogenous OA protects endothelial cells from SPION-induced oxidative stress and cell death independent of its incorporation into triglycerides.

A Versatile Interfacial Coassembly Method for Fabrication of Tunable Silica Shells with Radially Aligned Dual Mesopores on Diverse Magnetic Core Nanoparticles.

Anisotropic magnetic nanoparticles with a mesoporous silica shell have the combined merits of a magnetic core and a robust shell. Preparation of magnetically guidable core-shell nanostructures with a robust silica shell that contains well-defined, large, radially aligned silica pores is challenging, and hence this has rarely been described in detail. Herein, a dynamic soft-templating strategy is developed to controllably synthesize hierarchical, dual-mesoporous silica shells on diverse core nanoparticles, in terms of nanoparticle shape (i.e., spherical, chainlike, and disclike), magnetic properties (i.e., hard magnetic and superparamagnetic), and dimensions (i.e., from 3 nm to submicrometers). The developed interfacial coassembly method allows easy design of applicable silica shells containing tunable pore geometries with pore sizes ranging from below 5 nm to above 40 nm, with a specific surface area of 577 m2 g-1 and pore volume of 1.817 cm3 g-1. These are the highest values reported for magnetically guidable anisotropic nanoparticles. The versatility of the method is shown by transfer of the coating procedure to core particles as diverse as spherical superparamagnetic nanoparticles and their clusters as well as by ferromagnetic 3 nm thick hexaferrite nanoplatelets. This method can serve as a general approach for the fabrication of well-designed mesoporous silica coatings on a wide variety of core nanoparticles.

Magnetic Silica-Coated Iron Oxide Nanochains as Photothermal Agents, Disrupting the Extracellular Matrix, and Eradicating Cancer Cells.

Cancerous cells and the tumor microenvironment are among key elements involved in cancer development, progression, and resistance to treatment. In order to tackle the cells and the extracellular matrix, we herein propose the use of a class of silica-coated iron oxide nanochains, which have superior magnetic responsiveness and can act as efficient photothermal agents. When internalized by different cancer cell lines and normal (non-cancerous) cells, the nanochains are not toxic, as assessed on 2D and 3D cell culture models. Yet, upon irradiation with near infrared light, the nanochains become efficient cytotoxic photothermal agents. Besides, not only do they generate hyperthermia, which effectively eradicates tumor cells in vitro, but they also locally melt the collagen matrix, as we evidence in real-time, using engineered cell sheets with self-secreted extracellular matrix. By simultaneously acting as physical (magnetic and photothermal) effectors and chemical delivery systems, the nanochain-based platforms offer original multimodal possibilities for prospective cancer treatment, affecting both the cells and the extracellular matrix.

One-Pot Method for Preparation of Magnetic Multi-Core Nanocarriers for Drug Delivery.

The development of various magnetically-responsive nanostructures is of great importance in biomedicine. The controlled assembly of many small superparamagnetic nanocrystals into large multi-core clusters is needed for effective magnetic drug delivery. Here, we present a novel one-pot method for the preparation of multi-core clusters for drug delivery (i.e., magnetic nanocarriers). The method is based on hot homogenization of a hydrophobic phase containing a nonpolar surfactant into an aqueous phase, using ultrasonication. The solvent-free hydrophobic phase that contained tetradecan-1-ol, γ-Fe2O3 nanocrystals, orlistat, and surfactant was dispersed into a warm aqueous surfactant solution, with the formation of small droplets. Then, a pre-cooled aqueous phase was added for rapid cooling and the formation of solid magnetic nanocarriers. Two different nonpolar surfactants, polyethylene glycol dodecyl ether (B4) and our own N¹,N¹-dimethyl-N²-(tricosan-12-yl)ethane-1,2-diamine (SP11), were investigated for the preparation of MC-B4 and MC-SP11 magnetic nanocarriers, respectively. The nanocarriers formed were of spherical shape, with mean hydrodynamic sizes <160 nm, good colloidal stability, and high drug loading (7.65 wt.%). The MC-B4 nanocarriers showed prolonged drug release, while no drug release was seen for the MC-SP11 nanocarriers over the same time frame. Thus, the selection of a nonpolar surfactant for preparation of magnetic nanocarriers is crucial to enable drug release from nanocarrier.