Photo‐inactivation of bacteria in hospital effluent via thiolated iron‐doped nanoceria

Hospital wastewater is a major contributor of disease‐causing microbes and the emergence of antibiotic resistant bacteria. In this study, thiolated iron‐doped nanoceria was synthesised and tested for killing of microbes from hospital effluent. These particles were designed to inhibit the efflux pumps of the bacteria found in hospital effluent with further ability to activate in visible light via iron doping thus generating tunable amount of reactive oxygen species (ROS). The quantum yield of the ROS generated by the nanoceria was 0.67 while the ROS types produced were singlet oxygen (36%), hydroxyl radical (31%) and hydroxyl ions (32%), respectively. The particles were initially synthesised through green route using Foeniculum vulgare seeds extract and were annealed at 200°C and further coated with thiolated chitosan to enhance the solubility and efflux pump inhibition. X‐ray diffraction confirmed the polycrystalline nature of nanoparticles and uniform spherical shape with 30 nm size, confirmed by scanning electron microscope. The nanoparticles exhibited 100% bactericidal activity at 100 µg/mL against all the isolated bacteria. The enhanced bactericidal effect of iron‐doped nanoceria could be attributed to efflux inhibition via thiolated chitosan as well as the production of ROS upon illumination in visible light, causing oxidative stress against microbes found in hospital effluent.Inspec keywords: health and safety, chemical engineering, solubility, renewable materials, annealing, hospitals, antibacterial activity, cerium compounds, nanoparticles, photochemistry, wastewater treatment, iron, nanofabrication, microorganisms, X‐ray diffraction, effluents, scanning electron microscopy, particle size, diseasesOther keywords: antibiotic resistant bacteria, thiolated iron‐doped nanoceria, hospital effluent, visible light, reactive oxygen species, hydroxyl ions, thiolated chitosan, solubility, efflux pump inhibition, disease‐causing microbes, wastewater treatment, singlet oxygen, hydroxyl radical, Foeniculum vulgare seeds extract, annealing process, X‐ray diffraction, scanning electron microscopy, particle size, bactericidal activity, oxidative stress, photoinactivation, size 30.0 nm, temperature 200.0 degC, CeO₂ :Fe     

Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides

Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.     

Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage

The ability of engineered cerium oxide nanoparticles to confer radioprotection was examined. Human normal and tumor cells were treated with nanoceria and irradiated, and cell survival was measured. Treatment of normal cells conferred almost 99% protection from radiation-induced cell death, whereas the same concentration showed almost no protection of tumor cells. For the first time, nanoceria is shown to confer radioprotection to a normal human breast line but not to a human breast tumor line, MCF-7.     

Modeling the effect of oxygen on the amperometric response of immobilized organoselenium-based S-nitrosothiol sensors

Amperometric detection of S-nitrosothiols (RSNOs) at submicromolar levels in blood samples is of potential importance for monitoring endothelial function and other disease states that involve changes in physiological nitric oxide (NO) production. It is shown here that the elimination of dissolved oxygen from samples is critical when covalently attached diselenocystamine-based amperometric RSNO sensors are used for practical RSNO measurements. The newest generation of RSNO sensors utilizes an amperometric NO gas sensor with a thin organoselenium modified dialysis membrane mounted at the distal sensing tip. Sample RSNOs are catalytically reduced to NO within the dialysis membrane by the immobilized organoselenium species. In the presence of oxygen, the sensitivity of these sensors for measuring low levels of RSNOs (<μM) is greatly reduced. It is demonstrated that the main scavenger of the generated nitric oxide is not the dissolved oxygen but rather superoxide anion radical generated from the reaction of the reduced organoselenium species (the reactive species in the catalytic redox cycle) and dissolved oxygen. Computer simulations of the response of the RSNO sensor using rate constants and diffusion coefficients for the reactions involved, known from the literature or estimated from fitting to the observed amperometric response curves, as well as the specific geometric dimensions of the RSNO sensor, further support that nitric oxide and superoxide anion radical quickly react resulting in near zero sensor sensitivity toward RSNO concentrations in the submicromolar concentration range. Elimination of oxygen from samples helps improve sensor detection limits to ca. 10 nM levels of RSNOs.     

Effects of bioactive ceramics on the pathogenesis of rat vascular smooth muscle cells treated with phorbol 12-myristate 13-acetate

Vascular smooth muscle cells (VSMCs) play a pivotal role in vascular injury through proliferation and migration. Pro-inflammatory cytokines and cyclooxygenase (COX)-2 and nitric oxide synthase (NOS) are highly associated with the pathogenesis of VSMCs. We investigated the effect of bioactive ceramics on the expression of inflammatory cytokines, COX-2, and inducible NOS (iNOS) induced by phorbol 12-myristate 13-acetate (PMA) in rat VSMCs. The ceramics inhibited mRNA expression of IL-1β, TNF-α, IL-6, COX-2, and iNOS. Prostaglandin release was also diminished by the ceramics. The bioactive ceramics effect on cytokines, COX-2, and iNOS expression was achieved by inhibition of NF-κB activity. Interestingly, the ceramics-induced up-regulation of expression of endothelial NOS resulted in an increase of nitric oxide production. Thus, bioactive ceramics may have dual effects on the pathogenesis of VSMCs by regulation of NF-κB activity and NO production.     

Lipophilic NO-Driven Nanomotors as Drug Balloon Coating for the Treatment of Atherosclerosis

Drug-coated balloons (DCB) intervention is an important approach for the treatment of atherosclerosis (AS). However, this therapeutic approach has the drawbacks of poor drug retention and penetration at the lesion site. Here, a lipophilic drug-loaded nanomotor as a modified balloon coating for the treatment of AS is reported. First, a lipophilic nanomotor PMA-TPP/PTX loaded with drug PTX and lipophilic triphenylphosphine (TPP) compounds is synthesized. The PMA-TPP/PTX nanomotors use nitric oxide (NO) as the driving force, which is produced from the reaction between arginine on the motor substrate and excess reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in the AS microenvironment. The final in vitro and in vivo experimental results confirm that the introduction of the lipophilic drug-loaded nanomotor technology can greatly enhance the drug retention and permeability in atherosclerotic lesions. In particular, NO can also play an anti-AS role in improving endothelial cell function and reducing oxidative stress. The chemotherapeutic drug PTX loaded onto the nanomotors can inhibit cell division and proliferation, thereby exerting the effect of inhibiting vascular intimal hyperplasia, which is helpful for the multiple therapies of AS. Using nanomotor technology to solve cardiovascular diseases may be a promising research direction.     

Increased oxidative stress in foam cells obtained from hemodialysis patients

Premature atherosclerosis represents the main cause of mortality among end‐stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor‐α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by‐products were measured in the supernatants of macrophage‐derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by‐products, inducible nitric oxide synthase activity, and tumor necrosis factor‐α between patients and controls. Our results, obtained with human macrophages and macrophage‐derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions.     

Cerium Oxide Nanoparticles: Advances in Biodistribution,Toxicity, and Preclinical Exploration

Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well‐dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium‐oxide‐associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society.     

Near‐Infrared Upconversion Mesoporous Cerium Oxide Hollow Biophotocatalyst for Concurrent pH‐/H2O2‐Responsive O2‐Evolving Synergetic Cancer Therapy

Tumor hypoxia is typically presented in the central region of solid tumors, which is mainly caused by an inadequate blood flow and oxygen supply. In the conventional treatment of hypoxic human tumors, not only the oxygen‐dependent photodynamic therapy (PDT), but also antitumor drug‐based chemotherapy, is considerably limited. The use of direct oxygen delivering approach with oxygen‐dependent PDT or chemotherapy may potentiate the reactive oxygen species (ROS)‐mediated cytotoxicity of the drug toward normal tissues. Herein, a synergetic one‐for‐all mesoporous cerium oxide upconversion biophotocatalyst is developed to achieve intratumorally endogenous H₂O₂‐responsive self‐sufficiency of O₂ and near‐infrared light controlled PDT simultaneously for overcoming hypoxia cancer. Furthermore, the sufficient O₂ plays an important role in overcoming the chemotherapeutic drug‐resistant cancer caused by hypoxia, therefore inducing tumor cell apoptosis significantly.     

Spatiotemporal Catalytic Nanozymes Microneedle Patches with Opposite Properties for Wound Management

Reactive oxygen species (ROS)-mediated biological catalysis involves serial programmed enzymatic reactions and plays an important part against infectious diseases; while the spatiotemporal control of catalytic treatment to break the limitations of the disease microenvironment is challenging. Here, a novel spatiotemporal catalytic microneedles patch (CMSP-MNs) integrated with dual-effective Cu₂MoS₄ (CMS) and polydopamine (PDA) nanoparticles (NPs) for breaking microenvironment restrictions to treat wound infections is designed. Since CMS NPs are loaded in the needles, CMSP-MNs can catalytically generate diverse ROS to cause effective bacterial inactivation during bacterial infection process. Besides, PDA NPs are encapsulated in the backing layer, which facilitate ROS elimination and oxygen production for solving hypoxic problems in wound microenvironment and alleviating the expression of inflammatory factors during the inflammation process. Based on these features, it is demonstrated through cell and animal experiments that these nanozymes-integrated MNs patches can realize selective regulation of ROS level with bacterial inactivation and inflammatory treatment, resulting in minimized side effects of over-production ROS and effective anti-infected treatment. It is believed that the presented MNs can provide a new therapeutic strategy with spatiotemporal adjustable catalytic properties in biomedical areas.     

Nanoceria coating imperfections and their effect on the high-temperature oxidation resistance of a 304 stainless steel

The microemulsion method was employed in this work for synthesizing nanocrystalline cerium oxide particles. Average nanoparticle sizes of 3.45 nm were produced by these means. XPS determinations indicated that both Ce³⁺ and Ce⁴⁺ are present in the synthesized nanoceria particles, with an average amount of 22.8 % of Ce³⁺ ions. It was found that the nanocrystalline cerium oxide coatings lead to significant improvements (of 1–2 orders of magnitude) in the high-temperature oxidation resistance of 304 SS. In addition, it was found that by decreasing the nanoparticle mean size from 10 to 3.45 nm, the effect of the coating protection was drastically improved. The experimentally determined parabolic rate constants k _p at 1073 and 1273 K for 304 SS indicated a reduction of up to two orders of magnitude when nanoceria coatings with 3.45 nm in mean size were applied. Also, the scale thickness was reduced from 15 to 5 μm when oxidized at 1073 K for 442 h. Coatings with purchased nanoceria particles (10 nm) were not as effective as the coatings with synthesized nanoceria. Apparently, at increasing nanoceria sizes, the oxidation protection is significantly reduced. In addition, it was found that the method of dipping for coating 304 SS does not provide a uniform coverage with nanoceria particles. Fe-rich ‘islands’ develop during high-temperature oxidation indicating that some regions do not exhibit the protection that nanoceria can provide. In contrast, relatively thick-coating regions on the steel substrate exhibit minimal oxidation, and the resultant scale is fine grained and uniform.     

Clinically Approved Carbon Nanoparticles with Oral Administration for Intestinal Radioprotection via Protecting the Small Intestinal Crypt Stem Cells and Maintaining the Balance of Intestinal Flora

The exploration of an old drug for new biomedical applications has an absolute predominance in shortening the clinical conversion time of drugs for clinical application. In this work, carbon nanoparticles suspension injection (CNSI), the first clinically approved carbon nanoparticles in China, is explored as a new nano‐radioprotective agent for potent intestinal radioprotection. CNSI shows powerful radioprotective performance in the intestine under oral administration, including efficient free radical scavenging ability, good biosafety, high chemical stability, and relatively long retention time. For example, CNSI shows high reactive oxygen species (ROS) scavenging activities, which effectively alleviates the mitochondrial dysfunction and DNA double‐strand breaks to protect the cells against radiation‐induced damage. Most importantly, this efficient ROS scavenging ability greatly helps restrain the apoptosis of the small intestinal epithelial and crypt stem cells, which decreases the damage of the mechanical barrier and thus relieves radiation enteritis. Moreover, CNSI helps remove the free radicals in the intestinal microenvironment and thus maintain the balance of intestinal flora so as to mitigate the radiation enteritis. The finding suggests a new application of clinically approved carbon nanoparticles, which not only promotes the development of new intestinal radioprotector, but also has a great potential for clinical transformation.     

The Use of Nanoparticles to Deliver Nitric Oxide to Hepatic Stellate Cells for Treating Liver Fibrosis and Portal Hypertension

Polymeric nanoparticles are designed to transport and deliver nitric oxide (NO) into hepatic stellate cells (HSCs) for the potential treatment of both liver fibrosis and portal hypertension. The nanoparticles, incorporating NO donor molecules (S‐nitrosoglutathione compound), are designed for liver delivery, minimizing systemic delivery of NO. The nanoparticles are decorated with vitamin A to specifically target HSCs. We demonstrate, using in vitro and in vivo experiments, that the targeted nanoparticles are taken up specifically by rat primary HSCs and the human HSC cell line accumulating in the liver. When nanoparticles, coated with vitamin A, release NO in liver cells, we find inhibition of collagen I and α‐smooth muscle actin (α‐SMA), fibrogenic genes associated with activated HSCs expression in primary rat liver and human activated HSCs without any obvious cytotoxic effects. Finally, NO‐releasing nanoparticles targeted with vitamin A not only attenuate endothelin‐1 (ET‐1) which elicites HSC contraction but also acutely alleviates haemodynamic disorders in bile duct‐ligated‐induced portal hypertension evidenced by decreasing portal pressure (≈20%) and unchanging mean arterial pressure. This study clearly shows, for the first time, the potential for HSC targeted nanoparticle delivery of NO as a treatment for liver diseases with proven efficacy for alleviating both liver fibrosis and portal hypertension.     

Mechanistic Investigation of the Biological Effects of SiO2, TiO2, and ZnO Nanoparticles on Intestinal Cells

Silicon dioxide (SiO₂), titanium dioxide (TiO₂), and zinc oxide (ZnO) are currently among the most widely used nanoparticles (NPs) in the food industry. This could potentially lead to unintended exposure of the gastrointestinal tract to these NPs. This study aims to investigate the potential side‐effects of these food‐borne NPs on intestinal cells and to mechanistically understand the observed biological responses. Among the panel of tested NPs, ZnO NPs are the most toxic. Consistently in all three tested intestinal cell models, ZnO NPs invoke the most inflammatory responses from the cells and induce the highest intracellular production of reactive oxygen species (ROS). The elevated ROS levels induce significant damage to the DNA of the cells, resulting in cell‐cycle arrest and subsequently cell death. In contrast, both SiO₂ and TiO₂ NPs elicit minimum biological responses from the intestinal cells. Overall, the study showcases the varying capability of the food‐borne NPs to induce a cellular response in the intestinal cells. In addition to physicochemical differences in the NPs, the genetic landscape of the intestinal cell models governs the toxicology profile of these food‐borne NPs.     

Elevated anti-inflammatory effects of eicosapentaenoic acid based self-aggregated glycol chitosan nanoparticles

The formation of nanoparticles from eicosapentaenoic acid (EPA) is crucial to improving EPA's bioavailability and pharmacological properties, and widening its use in biomedical fields. In this study, we report EPA-conjugated glycol chitosan (GC) that can self-aggregate into core-shell nanoparticles. The EPA-GC nanoparticles were internalized into the cytosol of RAW 264.7 cells by endocytosis, which results in effective delivery of EPA to the cells. There were no differences in the cell viability after the treatment with EPA-GC nanoparticles. In the anti-inflammatory studies, the EPA-GC nanoparticles significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and interleukin-1 beta (IL-1 beta) secretion in RAW 264.7 cells. The anti-inflammatory effects of the EPA-GC nanoparticles were far better than those seen for EPA only. Given their excellent bio-physicochemical properties, it is expected that EPA-GC nanoparticles may have a potential for widening the use of EPA in biomedical fields and, in particular, the treatment of inflammatory diseases.     

Chiral Ruthenium Nanozymes with Self-Cascade Reaction Driven the NO Generation Induced Macrophage M1 Polarization Realizing the Lung Cancer “Cocktail Therapy”

Macrophages as the main cause of cancer immunosuppression, how to effectively induce macrophage M1 polarization remain the major challenge in lung cancer therapy. Herein, inspired by endogenous reactions, a strategy is proposed to coactivate macrophage M1 polarization by reactive oxygen species (ROS) and nitric oxide (NO) with self-autocatalytic cascade reaction. To enhance the generation of NO and ROS, NO Precursor-Arginine as capping agents for inducing synthesis two kinds of chiral ruthenium nanozyme (D/L-Arginine@Ru). Under the properties of Ru nanozymes through synchronously mimicking the activity of oxidase and nitric oxide synthase (NOS), chiral Ru nanozyme can rapidly generate ¹O₂ and O₂ at first stage, and then catalyze Arginine to produce sufficient NO, thus enhance macrophage M1 polarization to reverse tumor immunosuppression. Moreover, combination the antitumor activity of ¹O₂, NO, the chiral Ru nanozymes realize the “cocktail therapy” by inducing tumor cell apoptosis as well as ferroptosis. In addition, the chirality influences the bioactivity of Ru nanozymes that L-Arginine@Ru shows the better therapeutic effect with stronger catalytic activity and natural homology. It is hoped the high performance of chiral Ru nanozyme with “cocktail therapy” is an effective therapeutic reagent and can provide a feasible treatment strategy for tumor catalytic therapy.     

Development of Polymeric Nanoprobes with Improved Lifetime Dynamic Range and Stability for Intracellular Oxygen Sensing

A class of core‐shell nanoparticles possessing a layer of biocompatible shell and hydrophobic core with embedded oxygen‐sensitive platinum‐porphyrin (PtTFPP) dyes is developed via a radical‐initiated microemulsion co‐polymerization strategy. The influences of host matrices and the PtTFPP incorporation manner on the photophysical properties and the oxygen‐sensing performance of the nanoparticles are investigated. Self‐loading capability with cells and intracellular‐oxygen‐sensing ability of the as‐prepared nanoparticle probes in the range 0%–20% oxygen concentration are confirmed. Polymeric nanoparticles with optimized formats are characterized by their relatively small diameter (<50 nm), core‐shell structures with biocompatible shells, covalent‐attachment‐imparted leak‐free construction, improved lifetime dynamic range (up to 44 μs), excellent storage stability and photostability, and facile cell uptake. The nanoparticles’ small sensor diameter and core‐shell structure with biocompatible shell make them suitable for intracellular detection applications. For intracellular detection applications, the leak‐free feature of the as‐prepared nanoparticle sensor effectively minimizes potential chemical interferences and cytotoxicity. As a salient feature, improved lifetime dynamic range of the sensor is expected to enable precise oxygen detection and control in specific practical applications in stem‐cell biology and medical research. Such a feature‐packed nanoparticle oxygen sensor may find applications in precise oxygen‐level mapping of living cells and tissue.     

Effect of 8 MeV electron beam irradiation on the structural and optical properties of CeO2 nanoparticles

The effect of 8 MeV electron beam irradiation on the structural and optical properties of cerium oxide nanoparticles was investigated. Ceria nanoparticles were synthesized by chemical precipitation method, and characterized by X-ray diffraction, transmission electron microscopy, ultraviolet–visible, photoluminescence and Raman spectroscopy. Ultraviolet–visible absorption spectra, photoluminescence and Raman spectra of beam irradiated samples were modified, and shifted to blue region, which were attributed to quantum size effect. Systematic observations found that nonstoichiometry, defects and size reduction caused by beam irradiation have great influence on optical band gap, blue shift, photoluminescence and Raman band modifications. Moreover, electron beam irradiation is a suitable technique to enhance the structural and optical properties of nanoceria by controlling the particle size, which may lead to potentially useful technological applications.     

Shedding Light on Metal‐Based Nanoparticles in Zebrafish by Computed Tomography with Micrometer Resolution

Metal‐based nanoparticles are clinically used for diagnostic and therapeutic applications. After parenteral administration, they will distribute throughout different organs. Quantification of their distribution within tissues in the 3D space, however, remains a challenge owing to the small particle diameter. In this study, synchrotron radiation‐based hard X‐ray tomography (SRμCT) in absorption and phase contrast modes is evaluated for the localization of superparamagnetic iron oxide nanoparticles (SPIONs) in soft tissues based on their electron density and X‐ray attenuation. Biodistribution of SPIONs is studied using zebrafish embryos as a vertebrate screening model. This label‐free approach gives rise to an isotropic, 3D, direct space visualization of the entire 2.5 mm‐long animal with a spatial resolution of around 2 µm. High resolution image stacks are available on a dedicated internet page ( http://zebrafish.pharma-te.ch ). X‐ray tomography is combined with physico‐chemical characterization and cellular uptake studies to confirm the safety and effectiveness of protective SPION coatings. It is demonstrated that SRμCT provides unprecedented insights into the zebrafish embryo anatomy and tissue distribution of label‐free metal oxide nanoparticles.     

Ceria Nanoparticles Meet Hepatic Ischemia‐Reperfusion Injury: The Perfect Imperfection

The mononuclear phagocyte system (MPS, e.g., liver, spleen) is often treated as a “blackbox” by nanoresearchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, this imperfection is exploited by applying nano‐antioxidants with preferential liver uptake to directly prevent hepatic ischemia‐reperfusion injury (IRI), which is a reactive oxygen species (ROS)‐related disease. Ceria nanoparticles (NPs) are selected as a representative nano‐antioxidant and the detailed mechanism of preventing IRI is investigated. It is found that ceria NPs effectively alleviate the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro‐inflammatory cytokines are then significantly reduced and the recruitment and infiltration of neutrophils are minimized, which suppress subsequent inflammatory reaction involved in the liver. The protective effect of nano‐antioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.