Chenchen Li

Toxic effects of metal oxide nanoparticles and their underlying mechanisms

Nanomaterials have attracted considerable interest owing to their unique physicochemical properties. The wide application of nanomaterials has raised many concerns about their potential risks to human health and the environment. Metal oxide nanoparticles (MONPs), one of the main members of nanomaterials, have been applied in various fields, such as food, medicine, cosmetics, and sensors. This review highlights the bio-toxic effects of widely applied MONPs and their underlying mechanisms. Two main underlying toxicity mechanisms, reactive oxygen species (ROS)- and non-ROS-mediated toxicities, of MONPs have been widely accepted. ROS activates oxidative stress, which leads to lipid peroxidation and cell membrane damage. In addition, ROS can trigger the apoptotic pathway by activating caspase-9 and -3. Non-ROS-mediated toxicity mechanism includes the effect of released ions, excessive accumulation of NPs on the cell surface, and combination of NPs with specific death receptors. Furthermore, the combined toxicity evaluation of some MONPs is also discussed. Toxicity may dramatically change when nanomaterials are used in a combined system because the characteristics of NPs that play a key role in their toxicity such as size, surface properties, and chemical nature in the complex system are different from the pristine NPs.摘要纳米材料由于其独特的性质已经被广泛应用于很多领域, 但随着纳米材料的大规模制备和广泛应用, 它对环境以及人类的潜在危害越来越引起人们的重视. 金属氧化物纳米颗粒(MONPs)作为一类纳米材料大量地用于食品、医药、化妆品、传感器等领域. 因此, MONPs的生物毒性研究至关重要. 本文主要对目前应用最为广泛的几种MONPs (纳米二氧化钛、氧化锌、氧化铁等)生物毒性的研究及其毒性机理做了总结. MONPs导致毒性的机制有两个方面: ROS介导的毒性和非ROS介导的毒性. ROS激活氧化应激, 导致脂质过氧化, 引起细胞膜损伤, 此外, ROS可以激活caspase-9和caspase-3, 触发凋亡通路. 非ROS介导的毒性机制, 包括MONPs释放的离子引起的毒性, 纳米粒子在细胞表面的粘附以及与特定的死亡受体的相互作用. 此外, 由于当纳米材料处于一个复杂的体系中时, 它自身的性质, 包括尺寸、粒径、表面化学性质等都会发生变化, 我们对一些MONPs的复合毒性也做了讨论.

Caseinophosphopeptides cytoprotect human gastric epithelium cells against the injury induced by zinc oxide nanoparticles

Zinc oxide nanoparticles (ZnO NPs) are widely used as food additives, especially in nutritional foods. However, many reports have demonstrated their toxicity in humans and other biological systems. Our study has confirmed that ZnO NPs can induce apoptosis and oxidative damage on human gastric epithelium cells (GES-1). Caseinophosphopeptides (CPP) are also used as functional food additives that sequester prooxidant metals and scavenge free radicals. Herein, we investigate the combined cytotoxicity of ZnO NPs and CPP for the first time. The results show that CPP protects GES-1 cells from oxidative stress induced by ZnO NPs, decreases reactive oxygen species, diminishes the level of malondialdehyde, increases the content of glutathione and improves the activity of superoxide dismutase. Therefore, CPP can protect GES-1 cells against ZnO NP induced injury through the down-regulation of oxidative stress.

Tumor Cell-Specific Nuclear Targeting of Functionalized Graphene Quantum Dots In Vivo

Specific targeting of tumor tissues is essential for tumor imaging and therapeutics but remains challenging. Here, we report an unprecedented method using synthetic sulfonic-graphene quantum dots (sulfonic-GQDs) to exactly target the cancer cell nuclei in vivo without any bio- ligand modification, with no intervention in cells of normal tissues. The key factor for such selectivity is the high interstitial fluid pressure (IFP) in tumor tissues, which allows the penetration of sulfonic-GQDs into the plasma membrane of tumor cells. In vitro, the sulfonic-GQDs are repelled out of the cell membrane because of the repulsive force between negatively charged sulfonic-GQDs and the cell membranes which contributes to the low distribution in normal tissues in vivo. However, the plasma membrane-crossing process can be activated by incubating cells in ultrathin film culture medium because of the attachment of sulfonic-GQDs on cell memebranes. Molecular dynamics simulations demonstrated that, once transported across the plasma membrane, the negatively charged functional groups of these GQDs will leave the membrane with a self-cleaning function retaining a small enough size to achieve penetration through the nuclear membrane into the nucleus. Our study showed that IFP is a previously unrecognized mechanism for specific targeting of tumor cell nuclei and suggested that sulfonic-GQDs may be developed into novel tools for tumor-specific imaging and therapeutics.

Size, Shape, and Protein Corona Determine Cellular Uptake and Removal Mechanisms of Gold Nanoparticles

Size, shape, and protein corona play a key role in cellular uptake and removal mechanisms of gold nanoparticles (Au NPs). The 15 nm nanoparticles (NP1), the 45 nm nanoparticles (NP2), and the rod-shaped nanoparticles (NR) enter into cells via a receptor-mediated endocytosis (RME) pathway. The star-shaped nanoparticles (NS) adopt not only clathrin-mediated, but also caveolin-mediated endocytosis pathways. However, the 80 nm nanoparitcles (NP3) mainly enter into the cells by macropinocytosis pathway due to the big size. Furthermore, the results indicate that the presence of protein corona can change the uptake mechanisms of Au NPs. The endocytosis pathway of NP1, NP2, and NS changes from RME to macropinocytosis pathway and NR changes from RME to clathrin and caveolin-independent pathway under the non-fetal bovine serun (FBS)-coated condition. Both FBS-coated and non-FBS-coated of five types of Au NPs are released out through the lysosomal exocytosis pathway. The size, shape, and protein corona have an effect on the exocytosis ratio and amount, but do not change the exocytosis mechanism. The systematic study of the endocytosis and exocytosis mechanism of Au NPs with different sizes and shapes will benefit the toxicology evaluation and nanomedicine application of Au NPs.

Sulfonic-functionalized Graphene Quantum Dots as a Highly Efficient Fluorescent Probe for Fe(III) Ions Detection

Results: It was observed that the Fe ions could efficiently quench the fluorescence of sulfonic-GQDs. With the optimized conditions, the sulfonic-GQDs exhibit high sensitivity and selectivity for fluorescence probe to detect the Fe ions with the calibration curve displays linear regions over the range of 5-100 μM and a detection limit of 407 nM. In addition, sulfonic-GQDs fluorescent probe show very good selectivity of the Fe ions detection. There is no obvious interference with detect of Fe ions when in the simulated complex sysSulfonic-functionalized Graphene Quantum Dots as a Highly Efficient Fluorescent Probe for Fe(III) Ions Detection SDRP Journal of Computational Chemistry & Molecular Modelling (ISSN: 2473-6260)

Toxic effects of zinc oxide nanoparticles combined with vitamin C and casein phosphopeptides on gastric epithelium cells and the intestinal absorption of mice

Zinc oxide nanomaterials have become common food additives in recent years. Casein phosphopeptides (CPP) and vitamin C (VC) are used as functional food additives together with ZnO nanoparticles (ZnO NPs) in many commercial foods. Our previous studies showed that VC can increase the cytotoxicity induced by ZnO NPs both in vitro and in vivo, while CPP can have a cytoprotective effect against oxidative stress induced by ZnO NPs. However, the combined toxic effect of the three additives together in food is unknown. Herein, we have investigated the combined toxicity of ZnO NPs, CPP and VC by altering the sequence of their addition to clarify their toxic mechanisms in the composite systems. When the order of addition of the three materials changes, the cytotoxicity induced by the ZnO NPs changes due to the different concentrations of dissolved Zn ions in the different groups. We have also probed the intestinal absorption of Zn ions with an everted gut sac model. The amount of Zn2+ absorbed in the intestine in different composite systems also responds differently to the sequence of addition of the additives. VC is more powerful at controlling the synergistic toxic effect induced by ZnO NPs compared to the protective role of CPP in the combined systems.