our results revealed that GO and their surface proteins inhibit AβF by decreasing the kinetic reaction.
Protein fibrillation process (e.g., from amyloid beta (Aβ) and α-synuclein) is the main cause of several catastrophic neurodegenerative diseases such as Alzheimer's and Parkinson diseases. During the past few decades, nanoparticles (NPs) were recognized as one of the most promising tools for inhibiting the progress of the disease by controlling the fibrillation kinetic process; for instance, gold NPs have a strong capability to inhibit Aβ fibrillations. It is now well understood that a layer of biomolecules would cover the surface of NPs (so called "protein corona") upon the interaction of NPs with protein sources. Due to the fact that the biological species (e.g., cells and amyloidal proteins) "see" the protein corona coated NPs rather than the pristine coated particles, one should monitor the fibrillation process of amyloidal proteins in the presence of corona coated NPs (and not pristine coated ones). Therefore, the previously obtained data on NPs effects on the fibrillation process should be modified to achieve a more reliable and predictable in vivo results. Herein, we probed the effects of various gold NPs (with different sizes and shapes) on the fibrillation process of Aβ in the presence and absence of protein sources (i.e., serum and plasma). We found that the protein corona formed a shell at the surface of gold NPs, regardless of their size and shape, reducing the access of Aβ to the gold inhibitory surface and, therefore, affecting the rate of Aβ fibril formation. More specifically, the anti-fibrillation potencies of various corona coated gold NPs were strongly dependent on the protein source and their concentrations (10% serum/plasma (simulation of an in vitro milieu) and 100% serum/plasma (simulation of an in vivo milieu)).
Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade hypothesis. Then magnetic nanoparticles (MNPs) and recent works on their applications in AD, focusing on the superparamagnetic iron oxide nanoparticles (SPIONs), are reviewed. Furthermore, the amyloid−nanoparticle interaction is highlighted, with the scope to be highly considered by the scientists aiming for diagnostics and/or treatment of AD employing nanoparticles. Furthermore, recent findings on the "ignored" parameters (e.g., effect of protein "corona" at the surface of nanoparticles on amyloid-β (Aβ) fibrillation process) are discussed. KEYWORDS: Magnetic resonance imaging, SPION, amyloid-β, nanomedicine, nanotechnology A lzheimer's disease (AD) is named after Alois Alzheimer, who described the first case in a 55 year old female patient (i.e., Auguste Deter) in 1906. The description of Auguste's pathology was featured by lifelong deteriorating memory, speaking, physical, and social abilities. After her death, the autopsy revealed uniform brain atrophy, atherosclerosis changes in larger cerebral vessels, neuronal loss, and numerous small foci perceivable even without staining distributed over the entire cortex. It took over 70 years to reveal that those foci consist of aggregates of extracellular loads of small peptides called amyloid-β (Aβ), that are considered today one of the hallmarks of the disease. 1 AD is characterized by progressive deterioration of cognitive function, most commonly of memory, that increasingly interferes with patients' daily activities leading to loss of independency (for details, see http://www.alz.org/downloads/ facts_figures_2012.pdf). To date, no precise treatments have been clinically proven to avoid or prevent the progression of AD. Several different pharmacological agents can only ameliorate or provide temporary alleviation of the symptoms. 2 In this review, we introduce clinical aspects and characteristics of AD with a focus on the amyloid cascade hypothesis. Magnetic nanoparticles (MNPs), as promising theranosis tools, are introduced, and recent reports on the potential applications of superparamagnetic iron oxide nanoparticles (SPIONs) in AD are summarized. It is worthwhile to note that the SPIONs are known as promising theranosis candidates for AD, due to their biocompatibility, unique magnetic properties and multifunctional application capability. 3,4 The amyloid−nanoparticle interaction is highlighted, with the scope to be highly considered by the scientific community aiming for diagnostics and/or treatment of AD employing nanoparticles. Moreover, recent findings on the "ignored" parameters (e.g., the effect of protein "corona" at the surface of nanoparticles on Aβ fibrillation process) are discussed.
Because of their unique properties which are strongly dependent on the physicochemical properties of metal nanomaterials, noble metal nanostructures, particularly silver, have attracted much attention in the fields of electronics, chemistry, physics, biology, and medicine. Regarding biology and medical applications, silver nanoparticles (NPs) are recognized as a promising candidate to fight against resistant pathogens because of their significant antimicrobial activities. However, there are two major ignored issues with these NPs. First, the effect of various types of bacteria on antibacterial efficacy of silver NPs is ignored; second, there is no information on the pattern and compositions of both soft- and hard-corona proteins at the surface of NPs, which can define cellular responses to the NPs. In this article, the bacterial effect on the antibacterial capability of silver NPs with various geometries (i.e., sphere, wire, cube, and triangle) was probed; in this case, three different types of bacteria including Escherichia coli (E. coli), Bacillus subtilis, and Staphylococcus aureus were employed. The results showed that the type of bacteria can have quite a significant role in the definition of antibacterial efficacy of NPs, which has significant implications in the high yield design of NPs for antibacterial applications and will require serious consideration in the future. In addition, both soft- and hard-corona proteins were analyzed, and the effects of protein coated NPs on normal cells were evaluated. According to the results, the composition and thickness of protein coronas were strongly dependent on the physicochemical properties of silver NPs. We have found that the composition and thickness of the protein corona can evolve quite significantly as one passes from particle concentrations and shapes appropriate to in vitro cell studies to those present in in vivo studies, which has important implications for in vitro-in vivo extrapolations and will require more consideration in the future.
It is now well known that the interaction between nanoparticulate systems and biological fluids leads to deposition of various proteins onto the surface of the nanoparticles (NPs), hence, formation of a protein ''corona''. Arrangement of the associated proteins on the surface of NPs defines the in vivo response of material to the surrounding biologic environment. In order to predict the intercellular fate of NPs, therefore, it is essential to have an in-depth insight into the factors influencing the protein corona composition. While remarkable progress has been made in elucidating the factors that affect hard corona composition, the actual intercellular pathways that particles undertake in vivo and their dependence on the corona composition have not been investigated. In this study, we demonstrated that variation in plasma concentration can significantly change the biological fate of NPs, through alteration in the composition of the protein shell. For this purpose, sulfonated polystyrene and silica NPs were interacted with human plasma and fetal bovine serum in gradient concentrations. In contrast to the hard coronas formed under conventional static plasma conditions, large differences were observed in the amounts and affinities of proteins when particles were maintained under the plasma gradient conditions. This finding can help scientists to have a better understanding of the nanoparticle-cell interactions in vivo and elucidate the safety considerations for biomedical applications, resulting in nano-biomaterials that are ''safe by design''.
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