Transcriptional profiling identifies physicochemical properties of nanomaterials that are determinants of the in vivo pulmonary response

Abstract

We applied transcriptional profiling to elucidate the mechanisms associated with pulmonary responses to titanium dioxide (TiO2 ) nanoparticles (NPs) of different sizes and surface coatings, and to determine if these responses are modified by NP size, surface area, surface modification, and embedding in paint matrices. Adult C57BL/6 mice were exposed via single intratracheal instillations to free forms of TiO2 NPs (10, 20.6, or 38 nm in diameter) with different surface coatings, or TiO2 NPs embedded in paint matrices. Controls were exposed to dispersion medium devoid of NPs. TiO2 NPs were characterized for size, surface area, chemical impurities, and agglomeration state in the exposure medium. Pulmonary transcriptional profiles were generated using microarrays from tissues collected one and 28 d postexposure. Property-specific pathway effects were identified. Pulmonary protein levels of specific inflammatory cytokines and chemokines were confirmed by ELISA. The data were collapsed to 659 differentially expressed genes (P ≤ 0.05; fold change ≥ 1.5). Unsupervised hierarchical clustering of these genes revealed that TiO2 NPs clustered mainly by postexposure timepoint followed by particle type. A pathway-based meta-analysis showed that the combination of smaller size, large deposited surface area, and surface amidation contributes to TiO2 NP gene expression response. Embedding of TiO2 NP in paint dampens the overall transcriptional effects. The magnitude of the expression changes associated with pulmonary inflammation differed across all particles; however, the underlying pathway perturbations leading to inflammation were similar, suggesting a generalized mechanism-of-action for all TiO2 NPs. Thus, transcriptional profiling is an effective tool to determine the property-specific biological/toxicity responses induced by nanomaterials.

Surface modification does not influence the genotoxic and inflammatory effects of TiO2nanoparticles after pulmonary exposure by instillation in mice

“…The two TiO 2 NPs were equally cytotoxic and marginally damaged the hepatoblastoma C3A cell line in humans (33,34). In a recent study, the global gene expression in mouse lung was very similar for NRCWE-001 and -002 (3). In general, the pulmonary transcriptional responses to the two TiO 2 s were more similar to each other than to other TiO 2 NPs and TiO 2 -containing paint dusts (3).…”

“…A detailed description of the preparation was reported previously (34). Both particles have 10nm declared primary particle sizes, the Brunauer–Emmett–Teller (BET) analysis (BET) surface area for NRCWE-001 is 99 m 2 /g and 84 m 2 /g for NRCWE-002, respectively (3,34). …”

“…The total surface area of deposited NPs seems to be an important predictor of pulmonary inflammation and acute phase response (3,22–24). The role of surface modification and surface charge is less clear (3). …”

Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

“…Saa3 , Saa1 and Saa2 are all expressed in mouse lung tissue during a pulmonary acute phase response [9;27;29;70] with Saa3 as the most differentially expressed Saa gene. In the mouse liver, Saa1 and Saa2 are the predominant Saa isoforms.…”

Zinc oxide nanoparticle and bovine serum albumin interaction and nanoparticles influence on cytotoxicity in vitro

“…The cosmetics or environmental inhalation exposure to the different nanoparticles (NPs), makes a blood circulatory system to be one of the main interaction organs exposed to NPs or NPbased nanomaterials. Therefore, a more detailed understanding of the interactions between NPs and blood proteins may help to elucidate the potential risk of NPs [2].…”