The toxic effect of monodisperse amorphous silica particles studied on an in vitro model of the human air–blood barrier

Observation of interaction forces by investigation of the influence of eluent additives on the retention behavior of aqueous nanoparticle dispersions in asymmetrical flow field-flow fractionation.

The investigation and subsequent understanding of the interactions of nanomaterials with components of their surrounding media is important to be able to evaluate both potential use cases as well as potential risks for human health and for the environment. To investigate such interactions, asymmetrical flow field-flow fractionation (AF4) is an interesting analytical tool. This statement grounds on the fact that interactions of the analyte with the membrane and with components of the eluent are crucial for the retention behavior of the analyte within the field-flow fractionation (FFF) channel. Therefore, the investigation of the retention behavior provides an insight in the nature of the int…

Development of a triple-culture model of the alveolar-capillary barrier

Tuning the surface of nanoparticles: Impact of poly(2-ethyl-2-oxazoline) on protein adsorption in serum and cellular uptake

Item does not contain fulltext Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asym…

Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures

Abstract Background To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic response…

Flotillin-involved uptake of silica nanoparticles and responses of an alveolar-capillary barrier in vitro

AbstractDrug and gene delivery via nanoparticles across biological barriers such as the alveolar-capillary barrier of the lung constitutes an interesting and increasingly relevant field in nanomedicine. Nevertheless, potential hazardous effects of nanoparticles (NPs) as well as their cellular and systemic fate should be thoroughly examined. Hence, this study was designed to evaluate the effects of amorphous silica NPs (Sicastar) and (poly)organosiloxane NPs (AmOrSil) on the viability and the inflammatory response as well as on the cellular uptake mechanisms and fate in cells of the alveolar barrier. For this purpose, the alveolar epithelial cell line (NCI H441) and microvascular endothelial…

Uptake of polymeric nanoparticles in a human induced pluripotent stem cell-based blood-brain barrier model: Impact of size, material, and protein corona.

The blood–brain barrier (BBB) maintains the homeostasis of the central nervous system, which is one of the reasons for the treatments of brain disorders being challenging in nature. Nanoparticles (NPs) have been seen as potential drug delivery systems to the brain overcoming the tight barrier of endothelial cells. Using a BBB model system based on human induced pluripotent stem cells (iPSCs), the impact of polymeric nanoparticles has been studied in relation to nanoparticle size, material, and protein corona. PLGA [poly(lactic-co-glycolic acid)] and PLLA [poly(d,l-lactide)] nanoparticles stabilized with Tween® 80 were synthesized (50 and 100 nm). iPSCs were differentiated into human brain m…

Nanoparticle Size Is a Critical Physicochemical Determinant of the Human Blood Plasma Corona: A Comprehensive Quantitative Proteomic Analysis

In biological fluids, proteins associate with nanoparticles, leading to a protein "corona" defining the biological identity of the particle. However, a comprehensive knowledge of particle-guided protein fingerprints and their dependence on nanomaterial properties is incomplete. We studied the long-lived ("hard") blood plasma derived corona on monodispersed amorphous silica nanoparticles differing in size (20, 30, and 100 nm). Employing label-free liquid chromatography mass spectrometry, one- and two-dimensional gel electrophoresis, and immunoblotting the composition of the protein corona was analyzed not only qualitatively but also quantitatively. Detected proteins were bioinformatically cl…

High-resolution investigation of nanoparticle interaction with a model pulmonary surfactant monolayer.

The pulmonary surfactant film spanning the inner alveolar surface prevents alveolar collapse during the end-exhalation and reduces the work of breathing. Nanoparticles (NPs) present in the atmosphere or nanocarriers targeted through the pulmonary route for medical purposes challenge this biological barrier. During interaction with or passage of NPs through the alveolar surfactant, the biophysical functioning of the film may be altered. However, experimental evidence showing detailed biophysical interaction of NPs with the pulmonary surfactant film are scant. In this study, we have investigated the impact of a hydrophobic polyorganosiloxane (AmOrSil20) NPs on the integrity as well as on the …

Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins

Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 100-140 m(2) displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been c…

Influence of oscillating main flow on separation efficiency in asymmetrical flow field-flow fractionation.

The steadily rising interest in the investigation of interactions between nanomaterials and biological media has also led to an increasing interest in asymmetrical flow field-flow fractionation (AF-FFF). The biggest strength of AF-FFF is the possibility to alter the flow profiles to suit a specific separation problem. In this paper, the influence of an oscillating main flow on the separation efficiency of AF-FFF is investigated. Such oscillations can e.g. be caused by the main pump To investigate the influence of such flow conditions on the separation efficiency in AF-FFF systematically, different oscillation profiles were applied and their influence on the elution profile and the retention…