Background: Titanium dioxide (TiO₂) nanoparticles and fullerene (C₆₀) are two attractive manufactured nanoparticles with great promise in industrial and medical applications. However, little is known about the genotoxic response of TiO₂ nanoparticles and C₆₀ in mammalian cells. In the present study, we determined the mutation fractions induced by either TiO₂ nanoparticles or C₆₀ in gpt delta transgenic mouse primary embryo fibroblasts (MEF) and identified peroxynitrite anions (ONOO^-) as an essential mediator involved in such process. Results: Both TiO₂ nanoparticles and C₆₀ dramatically increased the mutation yield, which could be abrogated by concurrent treatment with the endocytosis inhibitor, Nystatin. Under confocal scanning microscopy together with the radical probe dihydrorhodamine 123 (DHR 123), we found that there was a dose-dependent formation of ONOO^- in live MEF cells exposed to either TiO₂ nanoparticles or C₆₀, and the protective effects of antioxidants were demonstrated by the nitric oxide synthase (NOS) inhibitor, N^G-methyl-L-arginine (L-NMMA). Furthermore, suppression of cyclooxygenase-2 (COX-2) activity by using the chemical inhibitor NS-398 significantly reduced mutation frequency of both TiO₂ nanoparticles and C₆₀. Conclusion: Our results provided novel information that both TiO₂ nanoparticles and C₆₀ were taken up by cells and induced kilo-base pair deletion mutations in a transgenic mouse mutation system. The induction of ONOO^- may be a critical signaling event for nanoparticle genotoxicity.

Selective targeting plus optimal biocompatibility is still a big challenge in nanomedicine. Although many nanomaterials including graphene oxide (GO) and molybdenum disulfide (MoS₂) have been tested for this purpose, these materials possess both favorable features and drawbacks, which hampers their further development. Herein, we prepared MoS₂/GO nanocomposites that manifested excellent dispersity in aqueous solutions and revealed acceptable biocompatibility in vitro and in vivo. Importantly, MoS₂/GO displayed a novel feature to selectively target the lung. In other words, MoS₂/GO manifested a pronounced tendency of localization towards the lung comparable to GO, offering a ‘guided missile’ effect in targeting the lung. Furthermore, MoS₂/GO composites possessed enhanced drug loading capacity together with reinforced tumor-killing efficacy against cancer cells that have the propensity to metastasize to the lung. Importantly, MoS₂/GO composites remarkably repressed metastatic tumor growth of B16 murine melanoma cancer cells in lungs of mice. Mechanistically, MoS₂/GO was demonstrated to reveal compromised reactions towards macrophages at the nano-bio interface relative to GO, which is accountable for the interaction and the uptake of nanosheets by macrophages associated with phagocytosis and macrophagic activation. Considered together, our findings established new MoS₂/GO nanocomposites with multi-functionalities including selective lung targeting, favorable drug loading capacity, elevated tumor killing efficacy and improved biocompatibility. Our study opens an avenue for MoS₂/GO nanocomposites in cancer nanotheranostics.

A diverse and large community of gut microbiota reside in the intestinal tract of various organisms and play important roles in metabolism and immune homeostasis of its host. The disorders of microbiota-host interaction have been closely associated with numerous chronic inflammatory and metabolic diseases, including inflammatory bowel disease and type 2 diabetes. The accumulating evidence has shown that fine particulate matter (PM2.5) exposure contributes to the diabetes, atherosclerosis and inflammatory bowel diseases; however, few studies have explored the impact of inhaled diesel PM2.5 on gut microbiota in vivo. In this study, C57BL/6J mice were exposed to diesel PM2.5 for 14 days via intratracheal instillation, and colon tissues and feces were harvested for microbiota analysis. Using high-throughput sequencing technology, we observed that intratracheally instillated diesel PM2.5 significantly altered the gut microbiota diversity and community. At the phylum and genus levels, principal coordinate analysis (PCoA) and principal component analysis (PCA) indicated pronounced segregation of microbiota compositions, which were further confirmed by β diversity analysis. As the most affected phylum, Bacteroidetes was greatly diminished by diesel PM2.5. On the genus level, Escherichia, Parabacteroides, Akkermansia, and Oscillibacter were significantly elevated by diesel PM2.5 exposure. Our findings provided clear evidence that exposure to diesel PM2.5 via intratracheal instillation deteriorated the gastrointestinal (GI) tract and significantly altered the structure and composition of gut microbiota, which might subsequently contribute to the developmental abnormalities of inflammation, immunity and metabolism.