Intracellular Reactive Oxygen Species Scavenging Research Articles

A shielded cascade of targeted nanocarriers spanning multiple microenvironmental barriers for inflammatory disease therapy

BackgroundThe multi-biological barriers present in the inflammatory microenvironment severely limit the targeted aggregation of anti-inflammatory drugs in the lesion area. However, conventional responsive drug carriers inevitably come into contact with several pro-responsive stimulatory mediators simultaneously, leading to premature drug release and loss of most therapeutic effects. Breaking through the multi-level barriers of the inflammatory microenvironment is essential to improve the enrichment and bioavailability of drugs.ResultsIn this study, we propose a novel two-stage structural strategy to build shielded cascades of targeted nanocarriers (FA-PTP@Que) through inflammatory mediators, using cascade structures to cross multiple environmental barriers. The cascade structure of FA-PTP@Que is responsive to inflammatory mediators and exhibits ideal pathological microenvironmental response and drug release properties. FA-PTP@Que has shown good macrophage regulation and anti-inflammatory effects by efficiently targeting macrophages, scavenging intracellular reactive oxygen species (ROS), and down-regulating the secretion of pro-inflammatory factors. Significantly, in mice with arthritis and colitis, FA-PTP@Que enriches and targets macrophages at the sites of arthritis and colitis, showing significant anti-inflammatory effects.ConclusionFA-PTP@Que combines active chemotaxis of nanocarriers to inflammatory tissues and active targeting of effector cells, acting precisely at each barrier level in different microenvironments by responding to inflammatory mediators and overcoming the multiple barriers in the inflammatory microenvironment. This innovative strategy can effectively break through various inflammatory microenvironments and has the potential application to other inflammatory diseases.

Self-Assembled EGCG Nanoparticles with Enhanced Intracellular ROS Scavenging for Skin Radioprotection.

Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application. To address this, we utilized epigallocatechin gallate (EGCG) as a model compound and employed nanotechnology to enhance cellular uptake of natural compounds, thereby improving their free radical scavenging capabilities. EGCG nanoparticles (EGCG NPs) with robust intracellular reactive oxygen species (ROS) scavenging ability were prepared via self-assembly. The morphology, size distribution, and antioxidant capacity of EGCG NPs were characterized. Cytocompatibility, intracellular ROS levels and DNA damage, cell migration and immune response of EGCG NPs to macrophages were tested in vitro. The in vivo radiation protection and biocompatibility of EGCG NPs were assessed in murine model. The EGCG NPs was successfully prepared and compared to free EGCG, EGCG NPs demonstrated better cellular uptake, significantly enhancing their biocompatibility, intracellular ROS scavenging capacity, and ability to mitigate DNA damage. Furthermore, EGCG NPs facilitated fibroblast proliferation and migration, while inhibiting the polarization of macrophages towards the M1 phenotype in vitro. In animal levels, EGCG NPs exhibited markedly improved radioprotective efficacy over free EGCG, effectively reducing skin edema and ulceration, alleviating pathological conditions such as interstitial edema, dermal fluid accumulation, and inflammatory infiltration, decreasing the duration of skin injury, and promoting wound healing. This work offers novel insights into the therapeutic application of EGCG NPs as a potential alternative for skin radioprotection and provides a powerful approach for developing radioprotective agents derived from natural products.

Inhalable multi-stimulus sensitive curcumin-alginate nanogels for scavenging reactive oxygen species and anti-inflammatory co-ordination to alleviate acute lung injury

Acute lung injury (ALI) is one of the most common and extremely critical clinical conditions, which progresses with an inflammatory response and overproduction of reactive oxygen species (ROS), leading to oxidative damage to the lungs. Curcumin (Cur) has great potential in treating ALI due to its excellent antioxidant and anti-inflammatory effects. In this study, Cur and alginate were cross-linked by zinc ions and intermolecular hydrogen bonding to form an inhalable aqueous nanogel system to overcome Cur's low solubility and bioavailability. Cur-alginate (ZA-Cur) nanogels exhibited superior antioxidant properties and down-regulated inflammation-associated factors in vitro with controlled-release behavior under multi-stimulus conditions such as temperature, pH, and ions. Meanwhile, the nanogels system could effectively scavenge cellular ROS to repair oxidative stress damage. In a mice model of ALI, tracheal nebulised inhalation of ZA-Cur nanogels down-regulated the expression of inflammation-related genes such as TNF-α, IL-1β, and IL-6, as well as modulated MDA content and CAT activity to attenuate oxidative stress injury, showing promising lung-protective effects. In conclusion, this work developed inhalable ZA-Cur nanogels to decelerate the progression of lesions in ALI by scavenging intracellular ROS and alleviating inflammation simultaneously, which may be a promising strategy for treating ALI.

Deodeokaloid, a New Indole Alkaloid N-Glycoside and Bioactive Phenolic Compounds from the Roots of Codonopsis lanceolata.

Codonopsis lanceolata, commonly known as the bonnet bellflower or deodeok, is primarily found in Eastern Asia. Its roots have been used traditionally across Asia to treat various ailments such as bronchitis, coughs, asthma, and inflammation. In our ongoing efforts to discover bioactive natural products, a phytochemical investigation of the n-BuOH fraction of C. lanceolata root extracts led to the isolation and identification of a new indole alkaloid N-glycoside, deodeokaloid (D-indole-3-lactic acid N-β-D-glucopyranoside) (1), alongside known compounds tangshenoside I (2), tangshenoside IV (3), and chlorogenic acid (4) through HPLC purification. The structure of the new compound 1 was elucidated using 1D and 2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Its absolute configuration was determined through a combination of DP4+ probability analysis and chemical reactions. The isolated compounds 1-4 were evaluated for their anti-Helicobacter pylori and antioxidant activities. In the anti-H. pylori assay, compound 3 showed antibacterial activity similar to that of quercetin as the positive control, inhibiting the bacterial growth by 36.8%. Compound 4 exhibited the most potent antioxidant activity, with an ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)] radical scavenging activity of 1624.7 mmol TE/mol and a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging capacity of 707.5 mmol Trolox equivalent (TE)/mol. Compounds 2-4 displayed significant intracellular reactive oxygen species (ROS) scavenging capacity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. This study highlights C. lanceolata roots as a promising natural source of bioactive compounds with potential therapeutic applications.

An injectable self-lubricating supramolecular polymer hydrogel loaded with platelet lysate to boost osteoarthritis treatment

Globally, osteoarthritis (OA) is the most prevalent joint disease and is characterized by infiltration of M1 macrophages in the synovium, anabolic–catabolic imbalance of the extracellular matrix (ECM), increased articular shear force and overproduction of reactive oxygen species (ROS). Disease-modifying OA drugs are not yet available, and treatments for OA focus solely on reducing pain and inflammation and have limited therapeutic effect. Herein, we developed an injectable self-lubricating poly(N-acryloyl alaninamide) (PNAAA) hydrogel loaded with platelet lysate (PL) (termed “PNAAA@PL”) for treating OA. Tribological and drug release tests revealed suitable lubrication properties and sustained release of bioactive factors in PNAAA@PL. In vitro experiments showed that PNAAA@PL alleviated interleukin-1β (IL-1β)-induced anabolic–catabolic imbalance of chondrocytes and repolarized pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype via intracellular ROS scavenging. Additionally, the PNAAA@PL hydrogel enhanced the migratory capacity and chemotaxis ability of stem cells, which are essential for chondrogenesis. In vivo, the functionalized PNAAA@PL hydrogel acted like synovial fluid following intra-articular injection into a rat OA model with anterior cruciate ligament transection, ultimately attenuating cartilage degeneration and synovitis. According to molecular mechanism studies, PNAAA@PL repairs cartilage in the OA model by inhibiting the NF-ĸB pathway. Overall, this self-lubricating PNAAA@PL hydrogel offers a comprehensive strategy for preventing OA progression by engineering a biophysiochemical microenvironment to generate high-quality hyaline cartilage.

Size and crystallinity effects on enzymatic activity and anti-inflammatory properties of cysteine-assisted Prussian blue nanozymes

Prussian blue nanoparticles (PB NPs) exhibit multiple enzymatic activities, such as superoxide dismutase-like, catalase-like, and peroxidase-like activities, which enable them to effectively scavenge reactive oxygen species (ROS) and demonstrate anti-inflammatory effects. To further enhance the enzymatic activity of PB NPs, it is crucial to explore the relationship between their physicochemical properties, such as size and crystallinity, and their enzymatic performance. In this study, PB NPs were synthesized using different pH levels and varying concentrations of cysteine (Cys) as a stabilizer. As the size decreases, crystallinity is gradually reduced, and defects increase. Cys-PB NPs with a smaller size and lower crystallinity exhibited high peroxidase-like activity, effectively reducing inflammation and scavenging intracellular ROS in vitro. Additionally, the stability of Cys-PB NPs plays a critical role in their anti-inflammatory properties, with higher stability favouring anti-inflammatory effect.

Carbon dots encapsulated zeolitic imidazolate framework-8 as an enhanced multi-antioxidant for efficient cytoprotection to HK-2 cells

Excessive reactive oxygen species (ROS) can lead to the imbalance of antioxidant system in the body and cause oxidative damage to cells. It is imperative to rationally design nanomaterials with high catalytic activity and multiple antioxidant activities. Here, line peppers-derived carbon dots (CDs) is encapsulated into zeolitic imidazolate framework-8 (CDs@ZIF-8) to achieve enhanced antioxidant activities for improved protective effect on cells. This nanosystem has a broad spectrum of antioxidant properties, which can effectively remove a variety of intracellular ROS and protect cells from ROS-induced death and cytoskeleton damage. In addition, CDs@ZIF-8 can reduce malondialdehyde (MDA) level and increase the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the level of glutathione (GSH) in human kidney proximal tubular epithelial cells (HK-2) cells. Mechanism studies demonstrated that CDs@ZIF-8 can up-regulate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), allowing the regulation of antioxidant enzymes to further achieve antioxidant effect. Besides, CDs@ZIF-8 inhibited the secretion of proinflammatory cytokines. This work demonstrates that the constructed CDs@ZIF-8 with multi-antioxidant activity can act as a highly efficient intracellular ROS scavenger and provide potential for the application in related oxidative stress-induced diseases.

ZIF-8@Pt Nanozyme Used for Scavenging Reactive Oxygen Species in the Treatment of Rheumatoid Arthritis

To formulate a ZIF-8 nano mimetic enzyme conjugated with platinum metal (ZIF-8@Pt) that can scavenge reactive oxygen species (ROS) and to explore its potential applications in the treatment of rheumatoid arthritis (RA). The ZIF-8@Pt nanozyme was created by in situ reduction. Characterization of the nanozyme was then performed and its ability to mimic enzymes was investigated. Cell experiments were conducted using RAW264.7 cells, which were divided into three groups, including the untreated group (UT), the positive control group receiving lipopolysaccharide (LPS), which was designated as the LPS group, and the ZIF-8@Pt group receiving ZIF-8@Pt and LPS treatment. The cell experiments were conducted to evaluate the anti-inflammatory properties of ZIF-8@Pt through scavenging intracellular ROS. On the other hand, a collagen-induced arthritis (CIA) model was induced in rats. Similar to the group designations in the cell experiments, the rats were assigned to three groups, including a healthy control group (the UT group), a positive control group receiving a local injection of PBS solution in the knee joint, which was referred to as the control group, and a treatment group receiving a local injection of ZIF-8@Pt solution in the knee joint, which was referred to as the ZIF-8@Pt group. General evaluation, imaging observation, assessment of inflammatory factors, and pathological evaluation were performed to assess the therapeutic efficacy of ZIF-8@Pt against RA. The in vitro experiment revealed significant difference in the levels of intracellular ROS and LPS-induced M1-type macrophage polarization between the LPS group and the ZIF-8@Pt group (P<0.05). The in vivo experiment showed that significant difference in the levels of inflammatory factors, including interleukin-1β (IL-1β), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and arginase-1 (Arg-1) in the knee joints of the CIA rats between the LPS group and the ZIF-8@Pt group (P<0.05). Comparing the findings for the ZIF-8@Pt group and the control group, pathology assessment revealed that ZIF-8@Pt reduced local hypoxia and suppressed osteoclastic activity, neovascularization, and M1-type macrophage polarization (P<0.05). The ZIF-8@Pt enzyme mimetic inhibits macrophage inflammatory polarization by ROS scavenging, thereby improving inflammation in RA. Furthermore, the ZIF-8@Pt nanozyme improves the hypoxic environment and inhibits angiogenesis and bone destruction, demonstrating promising therapeutic efficacy for RA.

Engineered Lipids for Intracellular Reactive Oxygen Species Scavenging in Steatotic Hepatocytes.

Intracellular reactive oxygen species (ROS) in steatotic cells pose a problem due to their potential to cause oxidative stress and cellular damage. Delivering engineered phospholipids to intracellular lipid droplets in steatotic hepatic cells, using the cell's inherent intracellular lipid transport mechanisms are investigated. Initially, it is shown that tail-labeled fluorescent lipids assembled into liposomes are able to be transported to intracellular lipid droplets in steatotic HepG2 cells and HHL-5 cells. Further, an antioxidant, an EUK salen-manganese derivative, which has superoxide dismutase-like and catalase-like activity, is covalently conjugated to the tail of a phospholipid and formulated as liposomes for administration. Steatotic HepG2 cells and HHL-5 cells incubated with these antioxidant liposomes have lower intracellular ROS levels compared to untreated controls and non-covalently formulated antioxidants. This first proof-of-concept study illustrates an alternative strategy to equip native organelles in mammalian cells with engineered enzyme activity.

Facile Preparation of Multifunctional Hydrogels with Sustained Resveratrol Release Ability for Bone Tissue Regeneration.

Injectable hydrogels show great promise for bone tissue engineering applications due to their high biocompatibility and drug delivery capabilities. The bone defects in osteoporosis are usually characterized by an oxidative and inflammatory microenvironment that impairs the regeneration capability of bone tissues. To attenuate the reactive oxygen species (ROS) and promote bone regeneration, an anti-oxidative hydrogel with osteogenic capacity was developed in this study. The poorly water soluble, natural antioxidant, resveratrol, was encapsulated in thiolated Pluronic F-127 micelles with over 50-times-enhanced solubility. The injectable hydrogel was facilely formed because of the new thioester bond between the free thiol group in modified F-127 and the arylate group in hyaluronic acid (HA)-acrylate. The resveratrol-loaded hydrogel showed good viscoelastic properties and in vitro stability and was cyto-compatible with bone-marrow-derived mesenchymal stem cells (BMSCs). The hydrogel allowed for a sustained release of resveratrol for at least two weeks and effectively enhanced the osteogenic differentiation of BMSCs by the up-regulation of osteogenic markers, including ALP, OCN, RUNX-2, and COL1. Moreover, the hydrogel exhibited anti-oxidative and anti-inflammatory abilities through the scavenging of intracellular ROS in RAW264.7 cells and inhibiting the gene expression and secretion of pro-inflammatory cytokines TNF-α and IL-1β under LPS exposure. In summary, the results suggest that our multifunctional hydrogel loaded with resveratrol bearing osteogenic, anti-oxidative, and anti-inflammatory actions is easily prepared and represents a promising resveratrol delivery platform for the repair of osteoporotic bone defects.

Mitochondria‐Targeted Polyphenol‐Cysteine Nanoparticles Regulating AMPK‐Mediated Mitochondrial Homeostasis for Enhanced Bone Regeneration

AbstractMitochondria are the energy source for basal cell functions as well as for tissue repair and regeneration. Excessive accumulation of reactive oxygen species (ROS) generated by bone tissue injury can cause cell oxidative stress and mitochondrial damage, negatively affecting osteogenic differentiation and tissue repair. However, efficient scavenging of mitochondrial ROS (mtROS) and restoration of mitochondrial homeostasis remain challenging. In this study, mitochondria‐targeted polyphenol/amino acid assembled nanoparticles (denoted as EC NPs) are constructed, which can achieve efficient intracellular ROS scavenging, especially for mtROS, recover the mitochondrial membrane potential, and enhance the inherent antioxidant system by increasing the antioxidase activity and GSH levels, following the re‐establishment of redox homeostasis. The EC NPs promoted AMPK‐mediated mitochondrial biogenesis, thereby providing more energy for osteogenic differentiation. Furthermore, the EC NPs not only recovered the osteogenic potential of the stem cells under oxidative stress but also demonstrated the ability to directly promote osteogenic differentiation by activating the cGMP‐PKG signaling pathway. In vivo experiments showed that the EC NPs significantly enhanced mitochondrial biogenesis and facilitated bone regeneration with a higher bone mass and bone mineral density. Thus, this multifunctional mitochondria‐targeted nanosystem represents a promising therapeutic strategy for bone regeneration based on mitochondrial homeostasis regulation.

Intracellular Trafficking Pathway and ROS Scavenging Activity of Glycol Chitosan‐Coated Cerium Oxide Nanoparticles in a Pathological AMD‐Like Model

AbstractAge‐related macular degeneration (AMD) is a degenerative eye disease that primarily affects the macula. AMD is a leading cause of vision loss in individuals over the age of 65, particularly more common in Caucasians than in other racial groups. Cerium oxide nanoparticles (CNPs) have emerged as highly promising nanomaterials in the treatment of AMD due to their potent antioxidant properties. In pathological damages of AMD conditions, characterized by oxidative stress resulting from an overproduction of reactive oxygen species (ROS), CNPs possess significant promise for attenuating the pathogenic processes and advancing therapeutic interventions. Despite their potential clinical applications, the widespread use of CNPs is greatly hampered by limited water solubility, and concerns have arisen about their potential impact on normal ROS production in mitochondria. Here, the antioxidative activity of glycol chitosan‐coated CNPs (namely, GCCNPs) and their behavior in mouse primary RPE (mRPE) cells are reported through an in vitro trafficking study. This findings demonstrate that GCCNPs effectively neutralize excessive ROS and prefer to exclusively accumulate in cytosol without any uptake in the nucleus and mitochondria of the mRPE cells. Moreover, GCCNPs demonstrated therapeutic effects by reducing the ROS level in a laser‐induced choroidal neovascularization (CNV) AMD‐like murine model.

Insights into the physiology, biochemistry, and metabolic pathways of ethanol-resistant marine microalgae in phytoplankton

Over two decades have passed since genetically modified prokaryotic cyanobacteria became capable of photosynthetically producing bioethanol. However, the limitation of low ethanol tolerance has impeded bioethanol production. In this study, the findings revealed that eukaryotic marine microalgae exhibited higher tolerance to ethanol compared to freshwater microalgae through a comparison of the growth performance of algal species under ethanol-induced stress. Specifically, the marine microalga Chlorella sp. MEM17 (MEM17) demonstrated tolerance to ethanol concentrations up to 6.0 % (v/v). Additionally, the polysaccharide and unsaturated fatty acid contents of MEM17 were considerably higher compared to ethanol-untreated control groups under ethanol stress. In conjunction with the comparative metabolomics approach, the remodeling of glycerophospholipid metabolic pathways was observed, specifically the conversion of a fraction of the reduced glycerophospholipids into specific glycerophospholipids, thereby enhancing the hindrance of ethanol entry into cells. The up-regulation of amino acid-related metabolic pathways aimed to augment the relative content of specific metabolites, such as gamma-aminobutyric acid (GABA), with the objective of scavenging intracellular reactive oxygen species (ROS). Furthermore, bolstered properties of the cell wall potentially facilitated by the increased polysaccharide content of MEM17 further impeded the potential entry of ethanol into the cell, while excess polysaccharide assisted in scavenging intracellular ROS. This study represents the first discovery of a high-concentration ethanol-tolerant eukaryotic marine microalga and its key metabolic pathways, with potential as “marine photosynthetic cell factories” for bioethanol production.

Fullerol-reinforced antioxidantive 3D-printed bredigite scaffold for accelerating bone healing

Reactive oxygen species play a vital role in tissue repair, and nonequilibrium of redox homeostasis around bone defect can compromise osteogenesis. However, insufficient antioxidant capacity and weak osteogenic performance remain major obstacles for bone scaffold materials. Herein, integrating the mussel-inspired polydopamine (PDA) coating and 3D printing technologies, we utilized the merits of both osteogenic bredigite and antioxidative fullerol to construct 3D-printed porous, biodegradable acid-buffering, reactive oxygen species (ROS) -scavenging and robust osteogenic bio-scaffold (denoted “FPBS”) for in situ bone defect restoration under oxidative stress microenvironment. Initially, fullerol nanoparticles were attached to the surface of the bredigite scaffold via covalently inter-crosslinking with PDA. Upon injury, extracellular ROS capturing triggered the oxidative degradation of PDA, releasing fullerol nanoparticles to enter into cells for further intracellular ROS scavenging. In vitro, FPBS had good biocompatibility and excellent antioxidative capability. Furthermore, FPBS promoted the osteogenesis of stem cells with significant elevation of osteogenic markers. Finally, in vivo implantation of FPBS remarkably enhanced new bone formation in a rat critical calvarial defect model. Overall, with amelioration of the ROS microenvironment of injured tissue and enhancement of osteogenic differentiation of stem cells simultaneously, FPBS may hold great potential towards bone defect repair.

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-1β 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.

Engineered Niobium Carbide MXenzyme-Integrated Self-Adaptive Coatings Inhibiting Periprosthetic Osteolysis by Orchestrating Osteogenesis-Osteoclastogenesis Balance.

Periprosthetic osteolysis induced by the ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles is a major complication associated with the sustained service of artificial joint prostheses and often necessitates revision surgery. Therefore, a smart implant with direct prevention and repair abilities is urgently developed to avoid painful revision surgery. Herein, we fabricate a phosphatidylserine- and polyethylenimine-engineered niobium carbide (Nb2C) MXenzyme-coated micro/nanostructured titanium implant (PPN@MNTi) that inhibits UHMWPE particle-induced periprosthetic osteolysis. The specific mechanism by which PPN@MNTi operates involves the bioresponsive release of nanosheets from the MNTi substrate within an osteolysis microenvironment, initiated by the cleavage of a thioketal-dopamine molecule sensitive to reactive oxygen species (ROS). Subsequently, functionalized Nb2C MXenzyme could target macrophages and escape from lysosomes, effectively scavenging intracellular ROS through its antioxidant nanozyme-mimicking activities. This further achieves the suppression of osteoclastogenesis by inhibiting NF-κB/MAPK and autophagy signaling pathways. Simultaneously, based on the synergistic effect of MXenzyme-integrated coatings and micro/nanostructured topography, the designed implant promotes the osteogenic differentiation of bone mesenchymal stem cells to regulate bone homeostasis, further achieving advanced osseointegration and alleviable periprosthetic osteolysis in vivo. This study provides a precise prevention and repair strategy of periprosthetic osteolysis, offering a paradigm for the development of smart orthopedic implants.

The MnO2/GelMA Composite Hydrogels Improve the ROS Microenvironment of Annulus Fibrosus Cells by Promoting the Antioxidant and Autophagy through the SIRT1/NRF2 Pathway.

Intervertebral disc degeneration (IVDD) is a worldwide disease that causes low back pain and reduces quality of life. Biotherapeutic strategies based on tissue engineering alternatives, such as intervertebral disc scaffolds, supplemented by drug-targeted therapy have brought new hope for IVDD. In this study, to explore the role and mechanism of MnO2/GelMA composite hydrogels in alleviating IVDD, we prepared composite hydrogels with MnO2 and methacrylate gelatin (GelMA) and characterized them using compression testing and transmission electron microscopy (TEM). Annulus fibrosus cells (AFCs) were cultured in the composite hydrogels to verify biocompatibility by live/dead and cytoskeleton staining. Cell viability assays and a reactive oxygen species (ROS) probe were used to analyze the protective effect of the composite hydrogels under oxidative damage. To explore the mechanism of improving the microenvironment, we detected the expression levels of antioxidant and autophagy-related genes and proteins by qPCR and Western blotting. We found that the MnO2/GelMA composite hydrogels exhibited excellent biocompatibility and a porous structure, which promoted cell proliferation. The addition of MnO2 nanoparticles to GelMA cleared ROS in AFCs and induced the expression of antioxidant and cellular autophagy through the common SIRT1/NRF2 pathway. Therefore, the MnO2/GelMA composite hydrogels, which can improve the disc microenvironment through scavenging intracellular ROS and resisting oxidative damage, have great application prospects in the treatment of IVDD.

Reinforcing Carrier‐Free Photothermal Nanodrugs Through Flavonol‐Driven Assembly

AbstractCarrier‐free nanodrugs that integrate chemodrugs and other therapeutic agents demonstrate good efficacy and minimized side effects, showing promise for combined therapy. However, a key challenge lies in enhancing the bioavailability and therapeutic potential of the nanodrugs through a controllable assembly process. Herein, a carrier‐free photothermal nanodrug (ZPQ NPs) is constructed through flavonol‐driven assembly with amine‐substituted perylene diimide for enhanced chemo‐photothermal combined cancer therapy. The flavonol, particularly quercetin, facilitates J‐aggregation of perylene diimide derivatives within the nanodrug and contributes to multiple improvements, including red‐shifted absorption, enhanced fluorescence intensity, improved photothermal conversion efficiency as well as excellent photostability. Moreover, the nanodrug also demonstrates enhanced cellular uptake and intracellular reactive oxygen species scavenging capability. The combination of quercetin and photothermal effect effectively kills cancer cells, as well as alleviates inflammation following photothermal therapy. Guided by in vivo fluorescence imaging, the application of ZPQ NPs results in complete tumor elimination and effectively inhibits tumor recurrence through chemo‐photothermal combined therapy. This work presents a straightforward strategy for constructing carrier‐free nanodrugs that exhibit simultaneous enhancements in both photophysical properties and biological activity.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal–organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.Graphical Schematic diagram showing the proposed mechanism that S@M@H NPs promoted diabetic wound healing

Evaluation of antioxidant activity and fermentation properties of potential probiotic strain Lactiplantibacillus plantarum HY7720 in plant-based materials

People on vegan diets are at risk of being deficient in varied nutrients such as vitamin B12 and certain amino acids. In this study, we investigated vitamin B12-producing lactic acid bacteria (LAB) as well as the probiotic and antioxidant properties. Lactiplantibacillus plantarum HY7720 was screened from 22 strains of LAB that were isolated from different plant foods, and its growth ability and extracellular vitamin B12-producing capacity in vitamin B12-deficient medium were investigated. To determine whether HY7720 functions as a probiotic, survival rate in the simulated gastrointestinal tract and adhesion property to human intestinal epithelial cells of HY7720 were compared with positive control, Lacticaseibacillus rhamnosus GG (LGG). Moreover, the results showed that HY7720 recovered the gene expression levels of tight junction-associated proteins (TJPs), including TJP1, TJP2, occludin (OCLN), and claudin-1 (CLDN1) and inhibited the secretion levels of pro-inflammatory cytokines, including interleukin (IL)-6 and IL-8, in tumor necrosis factor (TNF)-α-stimulated Caco-2 cells. Furthermore, we verified that HY7720 exhibit the antioxidant potential, by showing its intracellular reactive oxygen species (ROS) scavenging ability in hydrogen peroxide (H2O2)-stimulated Caco-2 cells. The ability of HY7720 to ameliorate H2O2-induced cytotoxicity in Caco-2 cells was inhibited by mitogen-activated protein kinase (MAPK) inhibitors, indicating that its antioxidant responses are related to extracellular signal-regulated kinase (ERK) and c-JUN N-terminal kinase (JNK). This study also investigated the nutritional qualities of three plant-based materials (brown rice, white rice, and soy milk) fermented using HY7720. Collectively, HY7720 could be used as a promising probiotic strain for the prevention of nutritional deficiencies among people on vegetarian diets.