Science-based evidence on pathways and effects of human exposure to micro- and nanoplastics.

Human exposure to plastic particles has raised great concern among all relevant stakeholders involved in the protection of human health due to the contamination of the food chain, surface waters, and even drinking water as well as due to their persistence and bioaccumulation. Now more than ever, it is critical that we understand the biological fate of plastics and their interaction with different biological systems. Because of the ubiquity of plastic materials in the environment and their toxic potential, it is imperative to gain reliable, regulatory-relevant, science-based data on the effects of plastic micro- and nanoparticles (PMNPs) on human health in order to implement reliable risk assessment and management strategies in the circular economy of plastics. This review presents current knowledge of human-relevant PMNP exposure doses, pathways, and toxic effects. It addresses difficulties in properly assessing plastic exposure and current knowledge gaps and proposes steps that can be taken to underpin health risk perception, assessment, and mitigation through rigorous science-based evidence. Based on the existing scientific data on PMNP adverse health effects, this review brings recommendations on the development of PMNP-specific adverse outcome pathways (AOPs) following the AOP Users' Handbook of the Organisation for Economic Cooperation and Development (OECD).

Particle surface functionalization affects mechanism of endocytosis and adverse effects of silver nanoparticles in mammalian kidney cells.

Silver nanoparticles (AgNPs) show a plethora of possible applications due to their antimicrobial properties. Different coatings of AgNPs are used in order to increase stability, availability, and activity. However, the question about the toxicity after prolonged exposure still remains. Here, we show that different surface coatings affect in vitro toxicity and internalization of AgNPs in porcine kidney (PK15) cells. AgNPs coated with cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP), sodium bis(2-ethylhexyl)-sulfosuccinate (AOT), poly-L-lysine (PLL), and bovine serum albumin (BSA) were toxic at the concentration of 10 mg Ag/L and higher. The toxicity increased in the following manner: PVP-AgNPs < CTAB-AgNPs < PLL-AgNPs < AOT-AgNPs < BSA-AgNPs. All types of AgNPs were internalized by the PK15 cells in a dose-dependent manner with greater internalization of AgNPs bearing positive surface charge. Transmission electron microscopy (TEM) experiments showed that AgNPs were located in the lysosomal compartments, while the co-treatment with known inhibitors of endocytosis pathways suggested macropinocytosis as the preferred internalization pathway. When inside the cell, all types of AgNPs induced the formation of reactive oxygen species while decreasing the concentration of the cell's endogenous antioxidant glutathione. The comet assay indicated possible genotoxicity of tested AgNPs starting at the concentration of 2 mg Ag/L or higher, depending on the surface functionalization. This study demonstrates the toxicity of AgNPs pointing to the importance of biosafety evaluation when developing novel AgNPs-containing materials.

Interaction of silver nanoparticles with plasma transport proteins: A systematic study on impacts of particle size, shape and surface functionalization.

Metallic nanoparticles are an important and widely used materials in development of nano-enabled medicine. For that reason, their interaction with biological molecules has to be systematically examined, as use of nanoparticles can lead to altered biological functions. In this study, we evaluated the interaction between silver nanoparticles (AgNPs) and two important plasma transport proteins - albumin and α-1-acid glycoprotein. To investigate comprehensively how different physico-chemical properties impact interaction of proteins with nanosurface, AgNPs of different size, shape and surface coating was prepared. The study was conducted using UV-Vis absorption, fluorescence, inductively coupled plasma mass spectrometry, circular dichroism spectroscopy, transmission electron microscopy, dynamic and electrophoretic light scattering techniques. The results showed significant complexities of the nano-bio interface and binding affinities of proteins onto surface of different AgNPs, which were affected by both AgNPs and protein properties. The most significant role on AgNPs-protein interaction had the coating agents used for AgNPs surface stabilization. Our findings should improve safe-by-design approach to development of the metallic nanomaterials for medical use.

Antimicrobial potency of differently coated 10 and 50 nm silver nanoparticles against clinically relevant bacteria Escherichia coli and Staphylococcus aureus.

Silver nanoparticles (nanoAg) are effective antimicrobials and promising alternatives to traditional antibiotics. This study aimed at evaluating potency of different nanoAg against healthcare infections associated bacteria: Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. A library of differently coated nanoAg of two different sizes (10 and 50 nm) were prepared using coating agents poly-L-Lysine (PLL), cetyltrimethyl-ammonium bromide (CTAB), citrate (CIT), polyvinyl-pyrrolidone (PVP), polysorbate 80 (Tween 80), and dioctyl-sodium sulfosuccinate (AOT). Stability evaluation by means of agglomeration and dissolution behaviour was performed for all nanoAg under conditions relevant for this study. Antibacterial properties of nanoAg were addressed by determining their minimal bactericidal concentrations (MBC) in deionised (DI) water to minimise the influence of silver speciation on its bioavailability. In parallel, AgNO3 was analysed as an ionic control. Studied nanoAg were efficient antimicrobials being remarkably more potent towards E. coli than to S. aureus (4 h MBC values for different nanoAg ranged from 0.08 to 5.0 mg Ag/L and 1.0-10 mg Ag/L, respectively). The toxicity of all nanoAg to S. aureus (but not to E. coli) increased with exposure time (4 h vs 24 h). 10 nm sized nanoAg released more Ag-ions and were more toxic than 50 nm nanoAg. Coating-dependent toxicity was more prominent for 50 nm nanoAg coated with Tween 80 or CTAB rendering the least toxic nanoAg. Obtained results showed that the antimicrobial effects of nanoAg were driven by shed Ag-ions, depended on target bacteria, exposure time and were the interplay of NP size, solubility and surface coating.

How protein coronas determine the fate of engineered nanoparticles in biological environment.

Nanomedicine is a booming medical field that utilises nanoparticles (NPs) for the development of medicines, medical devices, and diagnostic tools. The behaviour of NPs in vivo may be quite complex due to their interactions with biological molecules. These interactions in biological fluids result in NPs being enveloped by dynamic protein coronas, which serve as an interface between NPs and their environment (blood, cell, tissue). How will the corona interact with this environment will depend on the biological, chemical, and physical properties of NPs, the properties of the proteins that make the corona, as well as the biological environment. This review summarises the main characteristics of protein corona and describes its dynamic nature. It also presents the most common analytical methods to study the corona, including examples of protein corona composition for the most common NPs used in biomedicine. This knowledge is necessary to design NPs that will create a corona with a desired efficiency and safety in clinical use.

Surface coating affects behavior of metallic nanoparticles in a biological environment.

Silver (AgNPs) and maghemite, i.e., superparamagnetic iron oxide nanoparticles (SPIONs) are promising candidates for new medical applications, which implies the need for strict information regarding their physicochemical characteristics and behavior in a biological environment. The currently developed AgNPs and SPIONs encompass a myriad of sizes and surface coatings, which affect NPs properties and may improve their biocompatibility. This study is aimed to evaluate the effects of surface coating on colloidal stability and behavior of AgNPs and SPIONs in modelled biological environments using dynamic and electrophoretic light scattering techniques, as well as transmission electron microscopy to visualize the behavior of the NP. Three dispersion media were investigated: ultrapure water (UW), biological cell culture medium without addition of protein (BM), and BM supplemented with common serum protein (BMP). The obtained results showed that different coating agents on AgNPs and SPIONs produced different stabilities in the same biological media. The combination of negative charge and high adsorption strength of coating agents proved to be important for achieving good stability of metallic NPs in electrolyte-rich fluids. Most importantly, the presence of proteins provided colloidal stabilization to metallic NPs in biological fluids regardless of their chemical composition, surface structure and surface charge. In addition, an assessment of AgNP and SPION behavior in real biological fluids, rat whole blood (WhBl) and blood plasma (BlPl), revealed that the composition of a biological medium is crucial for the colloidal stability and type of metallic NP transformation. Our results highlight the importance of physicochemical characterization and stability evaluation of metallic NPs in a variety of biological systems including as many NP properties as possible.