Size-dependent cytotoxicity of gold nanoparticles

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.     

Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts

Nanoscale engineering is one of the most dynamically growing areas at the interface between electronics, physics, biology, and medicine. As there are no safety regulations yet, concerns about future health problems are rising. We investigated the effects of citrate/gold nanoparticles at different concentrations and exposure times on human dermal fibroblasts. We found that, as a result of intracellular nanoparticle presence, actin stress fibers disappeared, thereby inducing major adverse effects on cell viability. Thus, properties such as cell spreading and adhesion, cell growth, and protein synthesis to form the extracellular matrix were altered dramatically. These results suggest that the internal cell activities have been damaged.     

Interactions of human endothelial cells with gold nanoparticles of different morphologies

The interactions between noncancerous, primary endothelial cells and gold nanoparticles with different morphologies but the same ligand capping are investigated. The endothelial cells are incubated with gold nanospheres, nanorods, hollow gold spheres, and core/shell silica/gold nanocrystals, which are coated with monocarboxy (1-mercaptoundec-11-yl) hexaethylene glycol (OEG). Cell viability studies show that all types of gold particles are noncytotoxic. The number of particles taken up by the cells is estimated using inductively coupled plasma (ICP), and are found to differ depending on particle morphology. The above results are discussed with respect to heating efficiency. Using experimental data reported earlier and theoretical model calculations which take into account the physical properties and distribution of particles in the cellular microenvironment, it is found that collective heating effects of several cells loaded with nanoparticles must be included to explain the observed viability of the endothelial cells.     

Development and evaluation of fluorescent gold nanoparticles

Objective: It is difficult to identify the gold nanoparticles (AuNPs) intracellularly due to their non-fluorescent nature. Although gold can quench the fluorescence of any fluorophore, hence it is also difficult to combine gold with a fluorophore such as a semiconductor quantum dots (QDs). The aim of this study was to prepare a single fluorescent stable AuNPs combined with QDs (QDs-Au-NPs) which can be easily detected intracellularly.

Methods: QDs-Au-NPs were prepared via a simple one-step process through controlling the spacing between them using polyethylene glycol (PEG) as space linker in the form of PEGylated QDs. Furthermore, the applicability of this system was evaluated after coating the particles with somatostatin citrate, SST, to active target somatostatin receptors (SSTRs), and identification of the internalized particles via confocal laser scanning spectroscopy.

Results: The results showed that the produced Au shell has a thickness of 2.0?±?0.2?nm and QDs-Au-NPs showed the same fluorescence intensity compared to the unmodified QDs. Additionally, a stable monodisperse QDs-Au-NPs coated with SST were prepared after coating with 11-Mercaptoundecanoic acid. Moreover, cellular uptake study in Human Caucasian breast adenocarcinoma cell lines showed that QDs-Au-SST-NPs could be detected easily using the confocal microscope. In addition, they showed a significant (p?≤?.05) internalization per cell compared to untreated QDs-Au-NPs as detected by flow cytometry.

Conclusion: It could be concluded that the produced QDs-Au-NPs has a strong fluorescence property like QDs which enable them to be easily detected after cells internalization.     

纳米金与细胞相互作用机理的蛋白质组学研究

应用蛋白质组学结合生物信息学方法研究纳米金与人皮肤成纤维细胞(HDF-f )的作用机理.首先采用柠檬酸钠还原氛金酸法制备20nm的纳米金,然后应用MTT法和流式细胞术评价纳米金的细胞毒性及对细胞周期和细胞凋亡的影响.接着应用蛋白质组学技术和生物信息学方法筛选纳米金作用后细胞发生差异表达的蛋白质并进行基因本体论分析.MT...     

Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles

Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7) versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission electron microscopy (TEM) results show that cancer cells take up functional Glu-GNPs significantly more than naked GNPs. The TEM results also indicate that AET-capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs, or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48, and 72 hours. The results show that these functional GNPs have little or no toxicity to these cells. To validate the enhanced killing effect on cancer cells, various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to the cells, both with and without functional GNPs. By comparison with irradiation alone, the results show that GNPs significantly enhance cancer killing.     

Interaction of gold nanoparticles with proteins and cells

Abstract

Gold nanoparticles (Au NPs) possess many advantages such as facile synthesis, controllable size and shape, good biocompatibility, and unique optical properties. Au NPs have been widely used in biomedical fields, such as hyperthermia, biocatalysis, imaging, and drug delivery. The broad application range may result in hazards to the environment and human health. Therefore, it is important to predict safety and evaluate therapeutic efficiency of Au NPs. It is necessary to establish proper approaches for the study of toxicity and biomedical effects. In this review, we first focus on the recent progress in biological effects of Au NPs at the molecular and cellular levels, and then introduce key techniques to study the interaction between Au NPs and proteins. Knowledge of the biomedical effects of Au NPs is significant for the rational design of functional nanomaterials and will help predict their safety and potential applications.     

Inhibition of influenza virus infection by multivalent sialic-acid-functionalized gold nanoparticles

An efficient synthesis of sialic-acid-terminated glycerol dendron to chemically functionalize 2 nm and 14 nm gold nanoparticles (AuNPs) is described. These nanoparticles are highly stable and show high activity towards the inhibition of influenza virus infection. As the binding of the viral fusion protein hemagglutinin to the host cell surface is mediated by sialic acid receptors, a multivalent interaction with sialic-acid-functionalized AuNPs is expected to competitively inhibit viral infection. Electron microscopy techniques and biochemical analysis show a high binding affinity of the 14 nm AuNPs to hemagglutinin on the virus surface and, less efficiently, to isolated hemagglutinin. The functionalized AuNPs are nontoxic to the cells under the conditions studied. This approach allows a new type of molecular-imaging activity-correlation and is of particular relevance for further application in alternative antiviral therapy.     

The effect of size and shape of gold nanoparticles on thin film properties

This work describes the properties of gold nanoparticles (AuNPs) thin film on silicon (Si) substrates. The AuNPs can be divided into two major shapes: gold nanospheres (AuNSs) and gold nanorods (AuNRs). Two sizes of AuNSs (15 nm and 30 nm) and three aspect ratios of AuNRs (3.12, 3.39 and 3.60) were synthesised using the seeding-growth method. The AuNPs produced were deposited on Si substrates by using a spin-coating method followed by heat treatment at 200 °C. The number of AuNPs coatings varied as one, three and five coating depositions, respectively. From the field emission scanning electron microscopy, the AuNPs were uniformly distributed on the Si substrate surface. The AuNPs distribution increased with increasing number of AuNPs coating. Various deposited AuNPs with different shapes and sizes were analysed using current–voltage (I–V) measurement in light–dark conditions. The results showed that the resistance of samples became lower under light condition as the number of AuNPs coatings increased on the Si substrate due to the large amount of AuNPs particles, which had better properties in absorbing and scattering the light intensity. Among these samples, five-coating depositions of 15 nm AuNSs and 3.12 aspect ratio of AuNRs thin films gave the best sensitivity in light–dark condition. The higher sensitivity implied the better sensing and recovery properties since it can amplify a small signal from the same light source power/intensity.     

Soybeans as a phytochemical reservoir for the production and stabilization of biocompatible gold nanoparticles

The present study demonstrates an unprecedented green process for the production of gold nanoparticles by simple treatment of gold salts with soybean extracts. Reduction capabilities of antioxidant phytochemicals present in soybean and their ability to reduce gold salts chemically to nanoparticles with subsequent coating of proteins and a host of other phytochemicals present in soybean on the freshly generated gold nanoparticles are discussed. The new genre of green nanoparticles exhibit remarkable in vitro stability in various buffers including saline, histidine, HSA, and cysteine solutions. MTT assays reveal that the green gold nanoparticles are nontoxic and thus provide excellent opportunities for their applications in nanomedicine for molecular imaging and therapy. The overall strategy described herein for the generation of gold nanoparticles meets all 12 principles of green chemistry, as no "man-made" chemicals, other than the gold salts, are used in the green nanotechnological process.     

UV-photoactivation technique for size and shape controlled synthesis and annealing of stable gold nanoparticles in micelle

Gold nanoparticles of different sizes and shapes have been prepared by UV-photoactivation technique using the micelle TX-100 (poly(oxyethylene)iso-octylphenyl ether) as reducing agent, stabilizing agent as well as template which has been authenticated from the plasmon absorption band and TEM picture. The heating effect on those gold nanoparticles has also been studied.     

Gold Nanoparticles of Diameter 1.4 nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage

Gold nanoparticles (AuNPs) are generally considered nontoxic, similar to bulk gold, which is inert and biocompatible. AuNPs of diameter 1.4 nm capped with triphenylphosphine monosulfonate (TPPMS), Au1.4MS, are much more cytotoxic than 15‐nm nanoparticles (Au15MS) of similar chemical composition. Here, major cell‐death pathways are studied and it is determined that the cytotoxicity is caused by oxidative stress. Indicators of oxidative stress, reactive oxygen species (ROS), mitochondrial potential and integrity, and mitochondrial substrate reduction are all compromised. Genome‐wide expression profiling using DNA gene arrays indicates robust upregulation of stress‐related genes after 6 and 12 h of incubation with a 2 × IC50 concentration of Au1.4MS but not with Au15MS nanoparticles. The caspase inhibitor Z‐VAD‐fmk does not rescue the cells, which suggests that necrosis, not apoptosis, is the predominant pathway at this concentration. Pretreatment of the nanoparticles with reducing agents/antioxidants N‐acetylcysteine, glutathione, and TPPMS reduces the toxicity of Au1.4MS. AuNPs of similar size but capped with glutathione (Au1.1GSH) likewise do not induce oxidative stress. Besides the size dependency of AuNP toxicity, ligand chemistry is a critical parameter determining the degree of cytotoxicity. AuNP exposure most likely causes oxidative stress that is amplified by mitochondrial damage. Au1.4MS nanoparticle cytotoxicity is associated with oxidative stress, endogenous ROS production, and depletion of the intracellular antioxidant pool.     

纳米Au在蒙脱石层间的插层组装

以Na基蒙脱石为载体,分别以十二胺和PAA作为插层剂,利用此类插层剂可以捕捉金胶体的特点,使预先制备的金胶体插层于蒙脱石的层间制备组装型纳米金催化剂,并考察了高温焙烧对插层效果的影响。此外,以Au(en2)Cl3作为金的前驱体,研究了利用蒙脱石的阳离子交换特性直接进行纳米金插层组装的可行性。采用X射线衍射(XRD)、荧光分析(XRF)和透射电子显微镜(TEM)对所制备的样品进行了表征,结果表明:基于阳离子交换插层的制备方法未能实现纳米金的插层组装,金颗粒主要负载于蒙脱石片层的外表面,而基于配位俘获机理的插层组装方法所制备的纳米金在蒙脱石层间的插层组装效果良好,高温焙烧虽然导致层间纳米金的迁移,但金的粒径仍然保持在较低的尺寸范围。     

Receptor-mediated interactions between colloidal gold nanoparticles and human umbilical vein endothelial cells

A new strategy to manipulate cell operations is demonstrated, based on membrane-receptor-specific interactions between colloidal peptide-capped gold nanoparticles and human umbilical vein endothelial cells. It is shown that colloidal gold nanoparticles of similar charge and size but capped with different peptide sequences can deliberately trigger specific cell functions related to the important biological process of blood vessel growth known as angiogenesis. Specific binding of the peptide-capped particles to two endothelial-expressed receptors (VEGFR-1, NRP-1), which control angiogenesis, is achieved. The cellular fate of the functional nanoparticles is imaged and the influence of the different peptide-coated nanoparticles on the gene expression profile of hypoxia-related and angiogenic genes is monitored. The findings open up new avenues towards the deliberate biological control of cellular functions using strategically designed nanoparticles.     

Multiphoton molecular photorelease in click-chemistry-functionalized gold nanoparticles

Yellow-green controlled photorelease: probes click-linked to peptide-coated gold nanospheres by a triazole ring can be released in living cells under a focused 561 nm laser at low power. Photocleaving follows a three-photon event stimulated by the excitation of the localized surface plasmon resonance.