Xiumei Jiang

Mesoporous silica-coated gold nanorods as a light-mediated multifunctional theranostic platform for cancer treatment.

Mesoporous silica-coated gold nanorods (Au@SiO(2)) are developed as a promising and versatile theranostic platform for cancer treatment. Intracellular localization of Au@SiO(2) is visualized through two-photon imaging. With doxorubicin hydrochloride loaded, Au@SiO(2)-DOX show two light-mediated therapeutic modes: low power density laser-triggered drug release for chemotherapy, and high power density laser-induced hyperthermia, which suggest the potential for in-vivo applications.

Selective targeting of gold nanorods at the mitochondria of cancer cells: Implications for cancer therapy

We have observed that Au nanorods (NRs) have distinct effects on cell viability via killing cancer cells while posing negligible impact on normal cells and mesenchymal stem cells. Obvious differences in cellular uptake, intracellular trafficking, and susceptibility of lysosome to Au NRs by different types of cells resulted in selective accumulation of Au NRs in the mitochondria of cancer cells. Their long-term retention decreased mitochondrial membrane potential and increased reactive oxygen species level that enhances the likelihood of cell death. These findings thus provide guidance for the design of organelle-targeted nanomaterials in tumor therapy.

Revealing the binding structure of the protein corona on gold nanorods using synchrotron radiation-based techniques: understanding the reduced damage in cell membranes.

Regarding the importance of the biological effects of nanomaterials, there is still limited knowledge about the binding structure and stability of the protein corona on nanomaterials and the subsequent impacts. Here we designed a hard serum albumin protein corona (BSA) on CTAB-coated gold nanorods (AuNRs) and captured the structure of protein adsorption using synchrotron radiation X-ray absorption spectroscopy, microbeam X-ray fluorescent spectroscopy, and circular dichroism in combination with molecular dynamics simulations. The protein adsorption is attributed to at least 12 Au-S bonds and the stable corona reduced the cytotoxicity of CTAB/AuNRs. These combined strategies using physical, chemical, and biological approaches will improve our understanding of the protective effects of protein coronas against the toxicity of nanomaterials. These findings have shed light on a new strategy for studying interactions between proteins and nanomaterials, and this information will help further guide the rational design of nanomaterials for safe and effective biomedical applications.

Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity

Abstract Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemical species, and cytotoxicity of Ag NPs (15.9 ± 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a cell line recommended by the OECD for genotoxicity studies. Quantification of intracellular nanoparticle uptake and ion release was performed through inductively coupled plasma mass spectrometry. X-ray absorption near-edge structure (XANES) was employed to assess the chemical state of intracellular silver. The toxic potential of Ag NPs and Ag+ was evaluated by cell viability, reactive oxygen species (ROS) production and live–dead cell staining. The results suggest that cellular uptake of Ag NPs involves lipid-raft-mediated endocytosis and energy-independent diffusion. The degradation study shows that Ag NPs taken up into cells dissolved quickly and XANES results directly indicated that the internalized Ag was oxidized to Ag−O− species and then stabilized in silver−sulfur (Ag−S−) bonds within the cells. Subsequent cytotoxicity studies show that Ag NPs decrease cell viability and increase ROS production. Pre-incubation with N-acetyl-l-cysteine, an efficient antioxidant and Ag+ chelator, diminished the cytotoxicity caused by Ag NPs or Ag+ exposure. Our study suggests that the cytotoxicity mechanism of Ag NPs is related to the intracellular release of silver ions, followed by their binding to SH-groups, presumably coming from amino acids or proteins, and affecting protein functions and the antioxidant defense system of cells.

Multi-platform genotoxicity analysis of silver nanoparticles in the model cell line CHO-K1

Investigation of the genotoxic potential of nanomaterials is essential to evaluate if they pose a cancer risk for exposed workers and consumers. The Chinese hamster ovary cell line CHO-K1 is recommended by the OECD for use in the micronucleus assay and is commonly used for genotoxicity testing. However, studies investigating if this cell line is suitable for the genotoxic evaluation of nanomaterials, including induction of DNA adduct and micronuclei formation, are rare and for silver nanoparticles (Ag NPs) missing. Therefore, we here systematically investigated DNA and chromosomal damage induced by BSA coated Ag NPs (15.9±7.6 nm) in CHO-K1 cells in relation to cellular uptake and intracellular localization, their effects on mitochondrial activity and production of reactive oxygen species (ROS), cell cycle, apoptosis and necrosis. Ag NPs are taken up by CHO-K1 cells and are presumably translocated into endosomes/lysosomes. Our cytotoxicity studies demonstrated a concentration-dependent decrease of mitochondrial activity and increase of intracellular reactive oxygen species (ROS) in CHO-K1 cells following exposure to Ag NPs and Ag⁺ (0-20 μg/ml) for 24h. Annexin V/propidium iodide assay showed that Ag NPs and Ag⁺ induced apoptosis and necrosis, which is in agreement with an increased fraction of cells in subG1 phase of the cell cycle. Genotoxicity studies showed that Ag NPs but also silver ions (Ag⁺) induced bulky-DNA adducts, 8-oxodG and micronuclei formation in a concentration-dependent manner, however, there were quantitative and qualitative differences between the particulate and ionic form of silver. Taken together, our multi-platform genotoxicity and cytotoxicity analysis demonstrates that CHO-K1 cells are suitable for the investigation of genotoxicity of nanoparticles like Ag NPs.

Surface chemistry of gold nanorods: origin of cell membrane damage and cytotoxicity

We investigated how surface chemistry influences the interaction between gold nanorods (AuNRs) and cell membranes and the subsequent cytotoxicity arising from them in a serum-free cell culture system. Our results showed that the AuNRs coated with cetyl trimethylammonium bromide (CTAB) molecules can generate defects in the cell membrane and induce cell death, mainly due to the unique bilayer structure of CTAB molecules on the surface of the rods rather than their charge. Compared to CTAB-capped nanorods, positively charged polyelectrolyte-coated, i.e. poly(diallyldimethyl ammonium chloride) (PDDAC), AuNRs show improved biocompatibility towards cells. Thus, the present results indicate that the nature of surface molecules, especially their packing structures on the surface of AuNRs rather than surface charge, play a more crucial role in determining cytotoxicity. These findings about interfacial interactions could also explain the effects of internalized AuNRs on the structures or functions of organelles. This study will help understanding of the toxic nature of AuNRs and guide rational design of the surface chemistry of AuNRs for good biocompatibility in pharmaceutical therapy.

Silver nanoparticles – wolves in sheep's clothing?

Silver nanoparticles (Ag NPs) are one of the most widely utilized engineered nanomaterials (ENMs) in commercial products due to their effective antibacterial activity, high electrical conductivity, and optical properties. Therefore, they have been one of the most intensively investigated nanomaterials in terms of their toxic effects on humans and the environment. It has become clear during recent years that nanomaterials can behave unexpectedly due to new and unique characteristics when their particle size reaches the nanoscale (1–100 nm). Consequently, their effect on human health and the environment has been hard to predict. Widespread applications increase the chances of public and environmental exposure to Ag NPs and have thereby increased concerns regarding the potential adverse effects of Ag NPs on human health and environmental safety. To fully understand and predict possible health effects following exposure to Ag NPs, information about the mechanisms for their cytotoxicity and genotoxicity is necessary. The present paper attempts to review the cellular and molecular mechanisms behind Ag NP toxicity. In addition, the role of silver ions in the toxicity of Ag NPs is discussed.

Gold Nanomaterials: Preparation, Chemical Modification, Biomedical Applications and Potential Risk Assessment

Gold nanomaterials (Au NMs) have attracted increasing attention in biomedicine due to their facile preparation, multifunctional modifications, unique optical and electrical properties, and good biocompatibility. The physicochemical properties of Au NMs at nanoscale, like size, shape, surface chemistry, and near field effects, are rendering Au NMs potent candidates in biomedicine. Thus, risk assessment of negative effects of Au NMs on biological systems is becoming urgent and necessary for future applications. In this review, we summarize up-to-date progresses on the preparation and modification of Au NMs and their biomedical applications, including biosensor, bioimaging and phototherapy, gene/drug delivery. Finally, we discuss the potential risk of Au NMs to biological systems, which is instructive for rationally designing and preparing nanomaterials for safe applications in nanomedicine.

Osteogenesis of human induced pluripotent stem cells derived mesenchymal stem cells on hydroxyapatite contained nanofibers

Biomimetic nanofibrous scaffolds combined with stem cells are promising for bone tissue engineering. In the present study, we have employed nano-hydroxyapatite (nHAp) contained polycaprolactone (PCL) nanofibers as a biomimetic nanofibrous scaffold, and mesenchymal stem cells derived from human induced pluripotent stem cells (hiPS-MSCs) as the novel stem cells sources. The response of hiPS-MSCs on the nanofibrous scaffolds in terms of cell proliferation and differentiation into the osteoblastic phenotype was investigated by XTT assay, scanning electron microscopy (SEM), osteogenic genes expression (runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), collagen I (COL1A1), and osteocalcin (OC)), ALP activity, and calcium deposition. It is clearly shown that the hiPS-MSCs attached, and proliferated on the nanofibrous scaffolds. Compared with PCL nanofibers without nHAp, the cells on the nHAp contained nanofibers demonstrated superior capabilites to differentiate to form calcified extracellular matrix. Together with gene expression, all of the results indicate the great potential of the hiPS-MSCs seeded biomimetic nanofibrous scaffolds for bone regeneration in the future.

Ferroxidase-like activity of Au nanorod/Pt nanodot structures and implications for cellular oxidative stress

Platinum nanoparticles (NPs) are reported to mimic various antioxidant enzymes and thus may produce a positive biological effect by reducing reactive oxygen species (ROS) levels. In this manuscript, we report Pt NPs as an enzyme mimic of ferroxidase by depositing platinum nanodots on gold nanorods (Au@Pt NDRs). Au@Pt NDRs show pH-dependent ferroxidase-like activity and have higher activity at neutral pH values. Cytotoxicity results with human cell lines (lung adenocarcinoma A549 and normal bronchial epithelial cell line HBE) show that Au@Pt NDRs are taken up into cells via endocytosis and translocate into the endosome/lysosome. Au@Pt NDRs have good biocompatibility at NDR particle concentrations lower than 0.15 nΜ. However, in the presence of H2O2, lysosomelocated NDRs exhibit peroxidase-like activity and therefore increase cytotoxicity. In the presence of Fe2+, the ferroxidase-like activity of the NDRs protects cells from oxidative stress by consuming H2O2. Thorough consideration should be given to this behavior when employing Au@Pt NDRs in biological systems.