The in vitro and in vivo toxicity of gold nanoparticles
TL;DR: This review aims to provide a better understanding about the in vitro and in vivo toxicity of gold nanoparticles by reviewing and describing the up to date literatures related to this problem and it mainly focused on properties such as the particle size and shape, the surface charge and modification.
About: This article is published in Chinese Chemical Letters.The article was published on 2017-04-01. It has received 197 citations till now. The article focuses on the topics: Colloidal gold.
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TL;DR: Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted and their production methods, physicochemical characterization, and pharmacokinetics are reviewed.
Abstract: Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.
629 citations
TL;DR: In this paper, the authors highlight the recent development of smart drug delivery systems for a number of smart nanocarriers, including liposomes, micelles, dendrimers, meso-porous silica nanoparticles, gold nanoparticles and carbon nanotubes.
576 citations
TL;DR: The properties, applications and toxicity of metal and non-metal-based nanoparticles are reviewed and exposure to nanoparticles could induce the production of reactive oxygen species (ROS), which is a predominant mechanism leading to toxicity.
Abstract: Nanotechnology has recently found applications in many fields such as consumer products, medicine and environment Nanoparticles display unique properties and vary widely according to their dimensions, morphology, composition, agglomeration and uniformity states Nanomaterials include carbon-based nanoparticles, metal-based nanoparticles, organic-based nanoparticles and composite-based nanoparticles The increasing production and use of nanoparticles result in higher exposure to humans and the environment, thus raising issues of toxicity Here we review the properties, applications and toxicity of metal and non-metal-based nanoparticles Nanoparticles are likely to be accumulated in sensitive organs such as heart, liver, spleen, kidney and brain after inhalation, ingestion and skin contact In vitro and in vivo studies indicate that exposure to nanoparticles could induce the production of reactive oxygen species (ROS), which is a predominant mechanism leading to toxicity Excessive production of ROS causes oxidative stress, inflammation and subsequent damage to proteins, cell membranes and DNA ROS production induced by nanoparticles is controlled by size, shape, surface, composition, solubility, aggregation and particle uptake The toxicity of a metallic nanomaterial may differ depending on the oxidation state, ligands, solubility and morphology, and on environmental and health conditions
243 citations
TL;DR: In this paper, a review of strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach is presented and major challenges and future directions for the development of circRNA-based therapeutics are discussed.
Abstract: Significant progress has been made in circular RNA (circRNA) research in recent years. Increasing evidence suggests that circRNAs play important roles in many cellular processes, and their dysregulation is implicated in the pathogenesis of various diseases. CircRNAs are highly stable and usually expressed in a tissue- or cell type-specific manner. Therefore, they are currently being explored as potential therapeutic targets. Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies, respectively. These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems. Furthermore, recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner. While still in the early stages of development, the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency. In this review, we describe circRNA properties and functions and highlight their significance in disease. We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach. Lastly, we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.
151 citations
01 Jan 2020
TL;DR: This review not only provides a comprehensive summary on the mechanisms of inorganic nano-carrier based smart drug delivery systems but also summarizes their synthesis, applications, challenges and future possibilities.
Abstract: Tumor is a severe disease that affects human health. In addition to surgical treatment and radiotherapy, applying therapeutic agents that can kill the tumor directly or regulate immune systems is one of the most common treatments. The current problems of these therapeutic agents are lacking selective targeting of tumor and causing unfavorable side effects. In order to solve the problems and develop more effective medicines, nano-carriers are employed to fabricate smart drug delivery systems. In recent years, novel inorganic nano-materials, like mesoporous silica nanoparticles, gold nanoparticles, graphene oxide and black phosphorus, have shown talent in drug loading capacity, stability, and biocompatibility, which are becoming candidates for novel nano-carriers. This review not only provides a comprehensive summary on the mechanisms of inorganic nano-carrier based smart drug delivery systems but also summarizes their synthesis, applications, challenges and future possibilities.
138 citations
References
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TL;DR: The intracellular uptake of different sized and shaped colloidal gold nanoparticles is investigated and it is shown that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles.
Abstract: We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).
4,383 citations
TL;DR: It is argued that gold nanotechnology-enabled biomedicine is not simply an act of 'gilding the (nanomedicinal) lily', but that a new 'Golden Age' of biomedical nanotechnology is truly upon us.
Abstract: Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of ‘gilding the (nanomedicinal) lily’, but that a new ‘Golden Age’ of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).
2,712 citations
TL;DR: It is shown that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization and show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects.
Abstract: Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics1,2,3,4,5,6. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2–100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death)7, 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.
2,511 citations
TL;DR: This work investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells and developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines.
Abstract: We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require "controlling" NP accumulation rate. These studies will also have implications in determining nanotoxicity.
2,099 citations
TL;DR: A systematic study of water-soluble gold nanoparticles stabilized by triphenylphosphine derivatives ranging in size from 0.8 to 15 nm is made and the cytotoxicity of these particles in four cell lines representing major functional cell types with barrier and phagocyte function are tested.
Abstract: Gold nanoparticles are widely used in biomedical imaging and diagnostic tests. Based on their established use in the laboratory and the chemical stability of Au(0), gold nanoparticles were expected to be safe. The recent literature, however, contains conflicting data regarding the cytotoxicity of gold nanoparticles. Against this background a systematic study of water-soluble gold nanoparticles stabilized by triphenylphosphine derivatives ranging in size from 0.8 to 15 nm is made. The cytotoxicity of these particles in four cell lines representing major functional cell types with barrier and phagocyte function are tested. Connective tissue fibroblasts, epithelial cells, macrophages, and melanoma cells prove most sensitive to gold particles 1.4 nm in size, which results in IC(50) values ranging from 30 to 56 microM depending on the particular 1.4-nm Au compound-cell line combination. In contrast, gold particles 15 nm in size and Tauredon (gold thiomalate) are nontoxic at up to 60-fold and 100-fold higher concentrations, respectively. The cellular response is size dependent, in that 1.4-nm particles cause predominantly rapid cell death by necrosis within 12 h while closely related particles 1.2 nm in diameter effect predominantly programmed cell death by apoptosis.
1,707 citations