Project description:Gold nanoparticle (AuâNP) oligonucleotide complexes hold considerable promise as an approach for manipulating intracellular gene regulation. We show that the uptake and intracellular fate of AuâNP oligonucleotide complexes is associated with endocytosis and signal transduction. A transcriptomeâwide functional analysis of gene expression implicated multiple signaling pathways specific for AuâNP oligonucleotide complexes. In primary immune cells, the complexes trigger the expression of proâinflammatory nonâchemotactic cytokines rather than the many IFNâstimulated genes critical for induction of the immune response to a microbial challenge. Concordant with these changes, exposure to AuâNP oligonucleotide complexes is also accompanied by marked activation of immune cells. This distinct gene expression profile is not replicated in the lineageârestricted 293T cell line. These findings provide insight into the functional significance of the recruitment of AuâNP oligonucleotide complexes to endocytic structures and highlight the need to study the systems effects of nanomaterials in a biologically relevant model. We investigated the effect of AuâNP antisense EGFP oligonucleotide complexes on the transcriptome by expression profiling of 293T cells under four conditions and PBMCs under six conditions plus HIV infection with the Affymetrix U133 Plus 2.0 microarray. To control for experimental variability, three of the six PBMC conditions (24â and 48âhours after AuâNP oligonucleotide complex treatment, and the negative control) were assayed independently a second time (biological replicates) so that 13 microarrays were hybridized in total. A different batch of AuâNP oligonucleotide complexes was used in the generation of the four 293T and three replicate PBMC samples, and the microarrays for these samples were processed separately.
Project description:A transcriptome-wide functional analysis of gene expression implicated multiple signaling pathways specific for Au-NP oligonucleotide complexes. Exposure to Au-NP oligonucleotide complexes is also accompanied by marked activation of immune cells.
Project description:Nanometric revolution is underway, promising technical innovations in a wide range of applications, leading to a potential boost in environmental discharges. Nanoparticle propensity to be transferred throughout trophic chains and to generate toxicity was mainly assessed in primary consumers while a lack of knowledge for higher trophic levels persists. This study focused on a predatory fish, the European eel Anguilla anguilla exposed to gold nanoparticles (AuNP, 10 nm, PEG-coated) for 21 days at three concentration levels in food: 0 (NP0), 1 (NP1) and 10 (NP10) mg Au.kg-1 . Transfer was assessed by gold quantification in eel tissues and transcriptomic responses in the liver and brain were revealed by a high-throughput RNA-sequencing approach. Eels fed at NP10 presented an erratic feeding behaviour while gold quantification only indicated transfer to intestine and kidney of NP1 exposed eels. RNA-Sequencing was performed in NP0 and NP1 eels. A total of 258 genes and 156 genes were significantly differentially transcribed in response to AuNP trophic exposure in the liver and brain, respectively. Enrichment analysis highlighted modifications in the immune system-related processes in the liver. In addition, results pointed out a shared response of both organs regarding 13 genes, most of them being involved in immune functions. This finding may shed light into the mode of action and toxicity of AuNP in fish.
Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved single drug target therapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Proteomic and transcriptomic analyses revealed this direct cytotoxicity derived predominantly from Ab-mediated phagocytose, and the high affinity receptor for Fc gamma CD64 showed differential up-regulation only in gastric cancer cell treated by these nanodrugs compared with Ab, especially for AuNR group. This was the first time to discover that nanoparticle could induce regulation of immune related pathways and Fcγ receptor in the target cancer cell. Simplified and powerful designs of smart nanoparticles are highly desired for clinical. The dramatic enhancement of Ab accumulation with simple composition, combined with direct cytotoxic effect specific to cancer cells brought perfect therapeutic effects in vivo than Ab, which would promote further clinical application of gold nanorod in the diagnosis and therapeutics of gastric cancer.
Project description:ZnO nanoparticles can elicit a range of perturbed cell responses in vitro. The liver is a target for ZnO nanoparticle-, or Zn2+ released from ZnO nanoparticles-induced accumulation and/or impact in vitro and in vivo. The response of human hepatic stellate cells to ZnO nanoparticles has not yet been assessed. We aimed to determine whether the presence of surface coatings could protect human hepatic stellate cells from ZnO nanoparticle-induced cytotoxicity. Primary human hepatic stellate cells were treated with one of two types of uncoated ZnO nanoparticles (Z-COTE or Nanosun), two types of coated ZnO nanoparticles (HP1, MAX), a mass equivalent of ZnSO4, or were left untreated. After 24 h, RNA was isolated and processed for whole genome transcriptional profiling, comparing the expresson profiles of treated cells to the untreated controls. Each treatment was prepared in duplicate.
Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Transcriptomic and proteomic analyses revealed the mechanism of this direct cytotoxicity.