Mitochondrial Targeted Cerium Oxide Nanoclusters for Radiation Protection and Promoting Hematopoiesis.

Purpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection. Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF). Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway. Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.

Administration of ROS-Scavenging Cerium Oxide Nanoparticles Simply Mixed with Autoantigenic Peptides Induce Antigen-Specific Immune Tolerance against Autoimmune Encephalomyelitis.

The scavenging ability of cerium oxide nanoparticles (CeNPs) for reactive oxygen species has been intensively studied in the field of catalysis. However, the immunological impact of these particles has not yet been thoroughly investigated, despite intensive research indicating that modulation of the reactive oxygen species could potentially regulate cell fate and adaptive immune responses. In this study, we examined the intrinsic capability of CeNPs to induce tolerogenic dendritic cells via their reactive oxygen species-scavenging effect when the autoantigenic peptides were simply mixed with CeNPs. CeNPs effectively reduced the intracellular reactive oxygen species levels in dendritic cells in vitro, leading to the suppression of costimulatory molecules as well as NLRP3 inflammasome activation, even in the presence of pro-inflammatory stimuli. Subcutaneously administrated PEGylated CeNPs were predominantly taken up by antigen-presenting cells in lymph nodes and to suppress cell maturation in vivo. The administration of a mixture of PEGylated CeNPs and myelin oligodendrocyte glycoprotein peptides, a well-identified autoantigen associated with antimyelin autoimmunity, resulted in the generation of antigen-specific Foxp3+ regulatory T cells in mouse spleens. The induced peripheral regulatory T cells actively inhibited the infiltration of autoreactive T cells and antigen-presenting cells into the central nervous system, ultimately protecting animals from experimental autoimmune encephalomyelitis when tested using a mouse model mimicking human multiple sclerosis. Overall, our findings reveal the potential of CeNPs for generating antigen-specific immune tolerance to prevent multiple sclerosis, opening an avenue to restore immune tolerance against specific antigens by simply mixing the well-identified autoantigens with the immunosuppressive CeNPs.

Protective Role of Nanoceria-Infused Nanofibrous Scaffold toward Bone Tissue Regeneration with Senescent Cells.

The presence of oxidative stress in bone defects leads to delayed regeneration, especially in the aged population and patients receiving cancer treatment. This delay is attributed to the increased levels of reactive oxygen species (ROS) in these populations due to the accumulation of senescent cells. Tissue-engineered scaffolds are emerging as an alternative method to treat bone defects. In this study, we engineered tissue scaffolds tailored to modulate the adverse effects of oxidative stress and promote bone regeneration. We used polycaprolactone to fabricate nanofibrous mats by using electrospinning. We exploited the ROS-scavenging properties of cerium oxide nanoparticles to alleviate the high oxidative stress microenvironment caused by the presence of senescent cells. We characterized the nanofibers for their physical and mechanical properties and utilized an ionization-radiation-based model to induce senescence in bone cells. We demonstrate that the presence of ceria can modulate ROS levels, thereby reducing the level of senescence and promoting osteogenesis. Overall, this study demonstrates that ceria-infused nanofibrous scaffolds can be used for augmenting the osteogenic activity of senescent progenitor cells, which has important implications for engineering bone tissue scaffolds for patients with low regeneration capabilities.

Biogenesis of bacterial cellulose/xanthan/CeO2NPs composite films for active food packaging.

The increasing significance of biopolymer-based food packaging can be attributed to its biodegradability and independence from petroleum-derived materials. Concurrently, metal oxide nanoparticles (NPs) have gained prominence as effective antimicrobial agents against both wild-type and antibiotic-resistant microbes. In this study, cerium oxide or ceria, CeO2, nanoparticles with an average diameter of 50 nm were synthesized via a green method utilizing Vibrio sp. VLC cell lysate supernatant. The synthesized CeO2 NPs displayed remarkable antimicrobial properties, inhibiting the growth of Escherichia coli and Staphylococcus aureus by 93.7 % and 98 %, respectively. To enhance the potential of bacterial cellulose (BC) for advanced applications, we developed a BC/xanthan/CeO2 nanocomposite using both ex situ and in situ techniques. The integration of CeO2 NPs within the nanocomposite structure not only improved the inherent properties of BC, but also rendered it suitable for use in active food packaging systems. The nanocomposite exhibited no significant cytotoxicity on the human dermal fibroblast (HDF) cells, confirming its safety. Nanocomposites containing biogenically synthesized CeO2 NPs demonstrated exceptional efficacy for reducing microbial contamination. Bread samples coated with nanocomposite films displayed no signs of microbial growth. These results support the application of BC/xanthan/CeO2 nanocomposites as suitable and effective coating materials for antimicrobial food packaging applications.

NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging.

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Enhancing diabetic wound healing with a pH/glucose dual-responsive hydrogel for ROS clearance and antibacterial activity.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

Synergistic Therapeutic Effects of D-Mannitol-Cerium-Quercetin (Rutin) Coordination Polymer Nanoparticles on Acute Lung Injury.

Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.

Cerium Dioxide-Dextran Nanocomposites in the Development of a Medical Product for Wound Healing: Physical, Chemical and Biomedical Characteristics.

PURPOSE OF THE STUDY: the creation of a dextran coating on cerium oxide crystals using different ratios of cerium and dextran to synthesize nanocomposites, and the selection of the best nanocomposite to develop a nanodrug that accelerates quality wound healing with a new type of antimicrobial effect. MATERIALS AND METHODS: Nanocomposites were synthesized using cerium nitrate and dextran polysaccharide (6000 Da) at four different initial ratios of Ce(NO3)3x6H2O to dextran (by weight)-1:0.5 (Ce0.5D); 1:1 (Ce1D); 1:2 (Ce2D); and 1:3 (Ce3D). A series of physicochemical experiments were performed to characterize the created nanocomposites: UV-spectroscopy; X-ray phase analysis; transmission electron microscopy; dynamic light scattering and IR-spectroscopy. The biomedical effects of nanocomposites were studied on human fibroblast cell culture with an evaluation of their effect on the metabolic and proliferative activity of cells using an MTT test and direct cell counting. Antimicrobial activity was studied by mass spectrometry using gas chromatography-mass spectrometry against E. coli after 24 h and 48 h of co-incubation. RESULTS: According to the physicochemical studies, nanocrystals less than 5 nm in size with diffraction peaks characteristic of cerium dioxide were identified in all synthesized nanocomposites. With increasing polysaccharide concentration, the particle size of cerium dioxide decreased, and the smallest nanoparticles (<2 nm) were in Ce2D and Ce3D composites. The results of cell experiments showed a high level of safety of dextran nanoceria, while the absence of cytotoxicity (100% cell survival rate) was established for Ce2D and C3D sols. At a nanoceria concentration of 10-2 M, the proliferative activity of fibroblasts was statistically significantly enhanced only when co-cultured with Ce2D, but decreased with Ce3D. The metabolic activity of fibroblasts after 72 h of co-cultivation with nano composites increased with increasing dextran concentration, and the highest level was registered in Ce3D; from the dextran group, differences were registered in Ce2D and Ce3D sols. As a result of the microbiological study, the best antimicrobial activity (bacteriostatic effect) was found for Ce0.5D and Ce2D, which significantly inhibited the multiplication of E. coli after 24 h by an average of 22-27%, and after 48 h, all nanocomposites suppressed the multiplication of E. coli by 58-77%, which was the most pronounced for Ce0.5D, Ce1D, and Ce2D. CONCLUSIONS: The necessary physical characteristics of nanoceria-dextran nanocomposites that provide the best wound healing biological effects were determined. Ce2D at a concentration of 10-3 M, which stimulates cell proliferation and metabolism up to 2.5 times and allows a reduction in the rate of microorganism multiplication by three to four times, was selected for subsequent nanodrug creation.

Reactive oxide species and ultrasound dual-responsive bilayer microneedle array for in-situ sequential therapy of acute myocardial infarction.

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O2) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair.

Chemically Modulating Ceria-Based Artificial Haloperoxidase for Enhanced Antibacterial Activity and Biofilm Inhibition.

Ceria (CeO2) nanoparticles with haloperoxidase (HPO)-like activity have gained attention as a biologically benign antifoulant. 3,4-Dihydroxy-l-phenylalanine (DOPA), a main composition in mussel foot proteins, plays a crucial role in the biofouling process. However, the impact on the HPO-like activity and antifouling performance of CeO2 nanoparticles when DOPA molecules adsorb on them remains unexplored. This interesting question warrants investigation, particularly considering that it may occur in an actual marine environment. Herein, the interaction between DOPA and CeO2 is explored. Despite the higher Ce3+ fractions and the lower band gap energies due to the electron transfer from DOPA to the CeO2 surface, DOPA still had a slightly negative effect on the HPO-like activity of CeO2 since they decreased the exposed Ce3+ sites. The DOPA-CeO2 nanocomposites with HPO-like activities could kill bacteria and trigger quorum-sensing signaling quenching, achieving a biofilm inhibition performance. Amazingly, 0.1% DOPA-CeO2 nanocomposite exhibited higher antibacterial activity and better biofilm suppression activities due to its HPO-like activity and positive zeta potential. The remarkable results demonstrated that DOPA, as a participant in the biofouling process, could enhance the antibacterial activity and antifouling performance of CeO2 nanoparticles at an appropriate concentration.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model.

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.

Sorghum drought tolerance is enhanced by cerium oxide nanoparticles via stomatal regulation and osmolyte accumulation.

Sorghum [Sorghum bicolor (L.) Moench] yield is limited by the coincidence of drought during its sensitive stages. The use of cerium oxide nanoparticles in agriculture is minimal despite its antioxidant properties. We hypothesize that drought-induced decreases in photosynthetic rate in sorghum may be associated with decreased tissue water content and organelle membrane damage. We aimed to quantify the impact of foliar application of nanoceria on transpiration rate, accumulation of compatible solutes, photosynthetic rate and reproductive success under drought stress in sorghum. In order to ascertain the mechanism by which nanoceria mitigate drought-induced inhibition of photosynthesis and reproductive success, experiments were undertaken in a factorial completely randomized design or split-plot design. Foliar spray of nanoceria under progressive soil drying conserved soil moisture by restricting the transpiration rate than water spray, indicating that nanoceria exerted strong stomatal control. Under drought stress at the seed development stage, foliar application of nanoceria at 25 mg L-1 significantly improved the photosynthetic rate (19%) compared to control by maintaining a higher tissue water content (18%) achieved by accumulating compatible solutes. The nanoceria-sprayed plants exhibited intact chloroplast and thylakoid membranes because of increased heme enzymes [catalase (53%) and peroxidase (45%)] activity, which helped in the reduction of hydrogen peroxide content (74%). Under drought, compared to water spray, nanoceria improved the seed-set percentage (24%) and individual seed mass (27%), eventually causing a higher seed yield. Thus, foliar application of nanoceria at 25 mg L-1 under drought can increase grain yield through increased photosynthesis and reproductive traits.

Heat Waves Coupled with Nanoparticles Induce Yield and Nutritional Losses in Rice by Regulating Stomatal Closure.

The frequency, duration, and intensity of heat waves (HWs) within terrestrial ecosystems are increasing, posing potential risks to agricultural production. Cerium dioxide nanoparticles (CeO2 NPs) are garnering increasing attention in the field of agriculture because of their potential to enhance photosynthesis and improve stress tolerance. In the present study, CeO2 NPs decreased the grain yield, grain protein content, and amino acid content by 16.2, 23.9, and 10.4%, respectively, under HW conditions. Individually, neither the CeO2 NPs nor HWs alone negatively affected rice production or triggered stomatal closure. However, under HW conditions, CeO2 NPs decreased the stomatal conductance and net photosynthetic rate by 67.6 and 33.5%, respectively. Moreover, stomatal closure in the presence of HWs and CeO2 NPs triggered reactive oxygen species (ROS) accumulation (increased by 32.3-57.1%), resulting in chloroplast distortion and reduced photosystem II activity (decreased by 9.4-36.4%). Metabolic, transcriptomic, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed that, under HW conditions, CeO2 NPs activated a stomatal closure pathway mediated by abscisic acid (ABA) and ROS by regulating gene expression (PP2C, NCED4, HPCA1, and RBOHD were upregulated, while CYP707A and ALMT9 were downregulated) and metabolite levels (the content of γ-aminobutyric acid (GABA) increased while that of gallic acid decreased). These findings elucidate the mechanism underlying the yield and nutritional losses induced by stomatal closure in the presence of CeO2 NPs and HWs and thus highlight the potential threat posed by CeO2 NPs to rice production during HWs.

Multifunctional Nanocarrier for Synergistic Treatment of Alzheimer's Disease by Inhibiting ß-Amyloid Aggregation and Scavenging Reactive Oxygen Species.

The excessive depositions of ß-amyloid (Aß) and abnormal level of reactive oxygen species (ROS) are considered as the important pathogenic factors of Alzheimer's disease (AD). Strategies targeting only one of them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses the blood-brain barrier (BBB) efficiently was developed for inhibiting Aß aggregation and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their surfaces were grafted with cerium oxide nanoparticles (CeO2 NPs) and a short peptide K (CKLVFFAED). Living imaging showed that CICe@M-K was mainly distributed in the brain, liver, and kidneys, indicating CICe@M-K crossed BBB efficiently and accumulated in brain. After the irradiation of 808 nm laser, Cur was continuously released. Both of Cur and the peptide K can recognize and bind to Aß through multiple interaction including π-π stacking interaction, hydrophobic interaction, and hydrogen bond, inhibiting Aß aggregation. On the other hand, Cur and CeO2 NPs cooperate to relieve the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aß depositions, alleviate oxidative stress, and improve cognitive ability of the APP/PS1 AD mouse model, which demonstrated that CICe@M-K is a potential agent for AD treatment.

hCeO2@ Cu5.4O nanoparticle alleviates inflammatory responses by regulating the CTSB-NLRP3 signaling pathway.

Inflammatory responses, especially chronic inflammation, are closely associated with many systemic diseases. There are many ways to treat and alleviate inflammation, but how to solve this problem at the molecular level has always been a hot topic in research. The use of nanoparticles (NPs) as anti-inflammatory agents is a potential treatment method. We synthesized new hollow cerium oxide nanomaterials (hCeO2 NPs) doped with different concentrations of Cu5.4O NPs [the molar ratio of Cu/(Ce + Cu) was 50%, 67%, and 83%, respectively], characterized their surface morphology and physicochemical properties, and screened the safe concentration of hCeO2@Cu5.4O using the CCK8 method. Macrophages were cultured, and P.g-lipopolysaccharide-stimulated was used as a model of inflammation and co-cultured with hCeO2@Cu5.4O NPs. We then observe the effect of the transcription levels of CTSB, NLRP3, caspase-1, ASC, IL-18, and IL-1ß by PCR and detect its effect on the expression level of CTSB protein by Western blot. The levels of IL-18 and IL-1ß in the cell supernatant were measured by enzyme-linked immunosorbent assay. Our results indicated that hCeO2@Cu5.4O NPs could reduce the production of reactive oxygen species and inhibit CTSB and NLRP3 to alleviate the damage caused by the inflammatory response to cells. More importantly, hCeO2@Cu5.4O NPs showed stronger anti-inflammatory effects as Cu5.4O NP doping increased. Therefore, the development of the novel nanomaterial hCeO2@Cu5.4O NPs provides a possible new approach for the treatment of inflammatory diseases.

Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair.

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

Aß42 and ROS dual-targeted multifunctional nanocomposite for combination therapy of Alzheimer's disease.

Amyloid-ß (Aß) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aß aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer's disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aß42, we developed an Aß42 and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aß-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aß42 misfolding, accelerating Aß42 clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aß clearance exhibited by this Aß42 and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.

Enhancing stem cell therapy efficacy with functional lignin modified cerium-iron nanozyme through magnetic resonance imaging tracking and apoptosis protection in inflammatory environment.

Stem cell transplantation provides a promising approach for addressing inflammation and functional disorders. Nonetheless, the viability of these transplanted cells diminishes significantly within pathological environments, limiting their therapeutic potential. Moreover, the non-invasive tracking of these cells in vivo remains a considerable challenge, hampering the assessment of their therapeutic efficacy. Transition-metal oxide nanocrystals, known for their unique "enzyme-like" catalytic property and imaging capability, provide a new avenue for clinical application. In this study, the lignin as a biocompatible macromolecule was modified with poly (ethylene glycol) through chain-transfer polymerization, and then it was utilized to incorporate superparamagnetic iron oxide and cerium oxide nanocrystals creating a functional nanozyme. The iron oxide nanocrystals self-assembled into the hydrophobic core of nano system, while the in-situ mineralization of cerium oxide particles was carried out with the assistance of peripheral phenolic hydroxyl groups. The product, cerium­iron core-shell nanozyme, enabled effective stem cells labeling through endocytosis and exhibited catalase and superoxide dismutase activities within the cells. As a result, it could scavenge highly destructive hydroxyl radicals and peroxyl radicals, shielding stem cells from apoptosis in inflammatory environment and maintaining their differentiation ability. Additionally, when these functionalized stem cells were administered to mice with acute inflammation, not only did they alleviate disease symptoms, but they also allowed for the visualization using T2-weighted magnetic resonance imaging. This innovative therapeutic approach provides a new strategy for combatting diseases.

Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion.

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.