Protein Corona Modulates Distribution and Toxicological Effects of Silver Nanoparticles In Vivo

Barbir, Rinea; Goessler, Walter; Ćurlin, Marija; Micek, Vedran; Milić, Mirta; Vuković, Barbara; Milić, Marija; Ljubojević, Marija; Jurašin, Darija Domazet; Vrček, Ivana Vinković

doi:10.1002/ppsc.201900174

Cited by 21 publications

(24 citation statements)

References 69 publications

(126 reference statements)

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“…In the PBS, lower amount of free Ag + ions may be explained by the attachment of ionic Ag and Ag complex ions on the surface of AgNP agglomerates [ 15 , 16 ]. As expected, presence of proteins in PBS-hPBMC and protein corona formation on particle surface prevented significantly the dissolution of AgNPs in agreement with our previously published data [ 17 , 18 , 24 ]. Amount of free Ag + ions in this medium ranged between 0.1 and 0.4% ( v / v ) ( Table 2 ).…”

Section: Resultssupporting

confidence: 92%

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Surface Stabilization Affects Toxicity of Silver Nanoparticles in Human Peripheral Blood Mononuclear Cells

et al. 2020

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Silver nanoparticles (AgNPs) are one of the most investigated metal-based nanomaterials. Their biocidal activity boosted their application in both diagnostic and therapeutic medical systems. It is therefore crucial to provide sound evidences for human-related safety of AgNPs. This study aimed to enhance scientific knowledge with regard to biomedical safety of AgNPs by investigating how their different surface properties affect human immune system. Methods: preparation, characterization and stability evaluation was performed for four differently coated AgNPs encompassing neutral, positive and negative agents used for their surface stabilization. Safety aspects were evaluated by testing interaction of AgNPs with fresh human peripheral blood mononuclear cells (hPBMC) by means of particle cellular uptake and their ability to trigger cell death, apoptosis and DNA damages through induction of oxidative stress and damages of mitochondrial membrane. Results: all tested AgNPs altered morphology of freshly isolated hPBMC inducing apoptosis and cell death in a dose- and time-dependent manner. Highest toxicity was observed for positively-charged and protein-coated AgNPs. Cellular uptake of AgNPs was also dose-dependently increased and highest for positively charged AgNPs. Intracellularly, AgNPs induced production of reactive oxygen species (ROS) and damaged mitochondrial membrane. Depending on the dose, all AgNPs exhibited genotoxic potential. Conclusions: this study provides systematic and comprehensive data showing how differently functionalized AgNPs may affect the human immune system. Presented results are a valuable scientific contribution to safety assessment of nanosilver-based blood-contacting medical products.

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Section: Resultssupporting

confidence: 92%

“…In the case of PBS containing hPBMC, DLS and ELS experiments did not provide reliable data as the presence of cells increased significantly light scattering and shielded signals from AgNPs. In this case, dispersion of AgNPs were inspected visually, while protein corona formation was confirmed following protocol as described elsewhere [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Surface Stabilization Affects Toxicity of Silver Nanoparticles in Human Peripheral Blood Mononuclear Cells

et al. 2020

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“…However, one of the most significant challenges associated with the translation of theranostic nanomedicine to the clinic is the interaction between the nanomaterial and the tumor microenvironment [ 3 ]. In particular, when nanoparticles enter a biological system, their interaction with proteins can lead to the formation of a protein corona adsorbed on their surface via electrostatic, hydrophobic, and van der Waals forces [ 4 ], which can alter particle stability [ 5 , 6 ], dispersibility [ 7 , 8 ], biodistribution [ 9 ], pharmacokinetics [ 10 , 11 , 12 ], and the toxicity profile [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

et al. 2021

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The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high-resolution computed tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature, which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate-stabilized or passivated with bovine serum albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and inductively coupled plasma optical emission spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n = 8 mice/group). A significant difference is highlighted between citrate-GNP and BSA-GNP groups (** p < 0.005, Tukey’s multiple comparisons test), confirming that the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo, highlighting the spatial heterogeneity of the solid tumor.

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“…The membranes become thinner or corrode, causing damage to kidney cells [119]. Functional groups could be grafted to ENMs that could alter cytotoxicity [120]. In vivo experiments showed that PLGA-coated Fe 3 O 4 nanoparticles could enter cells through endocytosis and then be transported to lysosomes for degradation, which reduced the chance of contact with organelles.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Understanding of the Engineered Nanomaterial-Induced Toxicity on Kidney

Zhao

Zhan

et al. 2019

Journal of Nanomaterials

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With the rapid development of nanotechnology, engineered nanomaterials (ENMs) have been applied in many fields, such as food industry, biomedicine, and so on. However, the study on the health and safety implications of ENMs is still insufficient. Previous studies have shown that nanoparticles under acute or chronic exposure could be transported and accumulated in various organs and tissues, resulting in adverse effects or systemic toxicity. Among these, the kidney is one of the main organs that exposed ENMs will target through different routes. One of the important functions of the kidney is to discharge metabolic wastes and exogenous substances from the blood circulation of the whole body. During ENM exposure, the kidney may become vulnerable to toxicity. Studies have suggested that nanoparticles exposed to the kidney could provoke glomerular swelling, basilar membrane thickening, degeneration, and necrosis of renal tubular cells. These adverse effects of nanoparticles on the kidney may be related to their induced oxidative stress, inflammation, autophagy, DNA damage, and ER stress. This review aims to examine current studies on ENM-induced nephrotoxicity, with the focus on elucidating the potential molecular mechanisms of nanoparticle-induced toxicity on the kidney, which will further facilitate the safer design of ENMs and their applications.

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Protein Corona Modulates Distribution and Toxicological Effects of Silver Nanoparticles In Vivo

Cited by 21 publications

References 69 publications

Surface Stabilization Affects Toxicity of Silver Nanoparticles in Human Peripheral Blood Mononuclear Cells

Surface Stabilization Affects Toxicity of Silver Nanoparticles in Human Peripheral Blood Mononuclear Cells

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

Mechanistic Understanding of the Engineered Nanomaterial-Induced Toxicity on Kidney

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