Reactive Oxygen Species Scavenger Research Articles

Thermo-sensitive poly(amino acid) hydrogel mediates cytoprotection through an antioxidant mechanism

Oxidative stress, characterized by the excessive accumulation of reactive oxygen species (ROS), is linked to various pathological conditions, including myocardial infarction, cancer, and neurodegenerative diseases. Addressing ROS-induced cell damage has become a critical focus of biomedical research. In this study, a thermo-sensitive poly(amino acid) hydrogel, composed of poly(ethylene glycol)-block-poly(L-methionine), was prepared for cytoprotection through ROS scavenging. The sol-to-gel transition mechanism of the hydrogel was elucidated, and its potent antioxidant properties and cell protective effects were validated using hydrogen peroxide (H2O2)-induced oxidative stress and oxygen-glucose deprivation (OGD) models. The hydrogel significantly mitigated H2O2-induced damage in L929 cells, doubling their survival rate. Additionally, it scavenged approximately 35.8% of the ROS during OGD, reducing mitochondrial oxidative damage and resulting in a 29.4% decrease in apoptotic cell numbers. These findings underscore the potential biomedical applications of thermo-sensitive poly(amino acid) hydrogels, particularly in treating oxidative stress-related cell damage.

Ultraviolet-induced melanisation in lichens: physiological traits and transcriptome profile.

Lichens are important components of high-latitude boreal and Arctic habitats. While stress tolerant, they are among the most sensitive ecosystem components to climate change, in particular, an increase in ultraviolet light (UV) arising from polar ozone depletion and deforestation. This study is the first to explore the effects of UV-B on gene expression in lichens to predict metabolic pathways involved in tolerance. Using transcriptome profiling and bioinformatic analyses, here we studied the effects of UV-B on gene expression in lichens using Lobaria pulmonaria (L.) Hoff. as a model species. UV-B exposure causes significant browning of the upper cortex of the thallus, which correlates to an increased expression of biosynthetic gene clusters involved in the synthesis of eu- and allomelanins and melanin precursors. Based on transcriptome analyses, we suggest that the biosynthesis of melanins and other secondary metabolites, such as naphthalene derivates, tropolones, anthraquinones, and xanthones, is a trade-off that lichens pay to protect essential metabolic processes such as photosynthesis and respiration. Expression profiles of general stress-associated genes, in particular, related to reactive oxygen species scavenging, protection of proteins, and DNA repair, clearly indicate that the mycobiont is the more UV-B-responsive and susceptible partner in lichen symbiosis. Our findings demonstrate that UV-B stress activates an intricate gene network involved in tolerance mechanisms of lichen symbionts. Knowledge obtained here may enable the prediction of likely effects on lichen biodiversity caused by climate change and pollution.

Brassinosteroid improves resistance to phosphorus deficiency stress through regulating nutrient balance and reactive oxygen species scavenging in potato

Brassinosteroid (BR) plays a crucial role in plant growth, development and response to abiotic stress. However, the mechanism by which BR regulates the response of potato plants to phosphorus deficiency stress is still largely unknown. In this work, the effects of BR on the growth of potato plants under phosphorus deficient condition were investigated. Exogenous BR application mitigated the growth inhibition caused by phosphorus deficiency stress. Transcriptomic analyses revealed that BR application altered the expression of genes involved in mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, and nitrogen and phosphorus metabolisms under phosphorus deficient condition. Further gene ontology (GO) analysis indicated a significant enrichment of genes associated with reactive oxygen species scavenging process. Ectopic expression of potato brassinosteroid synthesis gene StCYP85A1 in Arabidopsis improved the resistance of transgenic plants to phosphorus deficiency stress, as indicated by the increased germination greening ratio and root growth. Quantitative real time PCR and antioxidant enzyme activity analysis revealed that ectopic expression of StCYP85A1 altered the expression of genes related to nitrogen and phosphorus metabolism, and promoted antioxidant enzyme activity in transgenic plants. These findings indicated that BR improved the tolerance of potato plants to phosphorus deficiency stress by regulating nutrient homeostasis and reactive oxygen species scavenging.

N-acetylcysteine, a small molecule scavenger of reactive oxygen species, alleviates cardiomyocyte damage by regulating OPA1-mediated mitochondrial quality control and apoptosis in response to oxidative stress.

Oxidative stress-induced mitochondrial damage is the major cause of cardiomyocyte dysfunction. Therefore, the maintenance of mitochondrial function, which is regulated by mitochondrial quality control (MQC), is necessary for cardiomyocyte homeostasis. This study aimed to explore the underlying mechanisms of N-acetylcysteine (NAC) function and its relationship with MQC. A hydrogen peroxide-induced oxidative stress model was established using H9c2 cardiomyocytes treated with or without NAC prior to oxidative stress stimulation. Autophagy with light chain 3 (LC3)-green fluorescent protein (GFP) assay, reactive oxygen species (ROS) with the 2',7'-dichlorodi hydrofluorescein diacetate (DCFH-DA) fluorescent, lactate dehydrogenase (LDH) release assay, adenosine triphosphate (ATP) content assay, and a mitochondrial membrane potential detection were used to evaluate mitochondrial dynamics in H2O2-treated H9c2 cardiomyocytes, with a focus on the involvement of MQC regulated by NAC. Cell apoptosis was analyzed using caspase-3 activity assay and Annexin V-fluorescein isothiocyanate (V-FITC)/propidium iodide (PI) double staining. We observed that NAC improved cell viability, reduced ROS levels, and partially restored optic atrophy 1 (OPA1) protein expression under oxidative stress. Following transfection with a specific OPA1-small interfering RNA, the mitophagy, mitochondrial dynamics, mitochondrial functions, and cardiomyocyte apoptosis were evaluated to further explore the mechanisms of NAC. Our results demonstrated that NAC attenuated cardiomyocyte apoptosis via the ROS/OPA1 axis and protected against oxidative stress-induced mitochondrial damage via the regulation of OPA1-mediated MQC. NAC ameliorated the injury to H9c2 cardiomyocytes caused by H2O2 by promoting the expression of OPA1, consequently improving mitochondrial function and decreasing apoptosis.

Effects and medical application of plant-origin polyphenols: A narrative review

The impact of oxidative stress in the pathogenesis of various diseases is well known. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of a biological system to detoxify these reactive intermediates or repair the resulting damage. Polyphenols, a diverse group of compounds with antioxidant properties, help reduce damage by ROS. They are abundant in fruits, vegetables, tea, coffee, wine, and other plant-based foods. The mechanisms of their antioxidant activity are related to their ability to regulate cellular signaling pathways, metal chelation, and mitochondrial protection, while modulating antioxidant enzyme activity and exhibiting anti-inflammatory effects. Polyphenols can also reduce oxidative stress through ROS scavenging, direct neutralization, or enhancing antioxidant defenses within cells. It has been established that polyphenols derived from plant compounds do not harm the metabolism of normal cells, but are involved in modulating the metabolic pathways of diseased cells, which is related to their high redox sensitivity. Incorporating polyphenol-rich foods into the diet is beneficial for maintaining overall health and reducing the risk of oxidative stress-related diseases. Researchers are exploring the therapeutic potential of polyphenols as dietary supplements or functional foods in medical applications. This review discusses the origin, structure, benefits, and application of plant polyphenols in medicine and the food industry. Keywords: biologically active compounds, polyphenols, oxidative stress, antioxidant activity, functional food.

Improving treatment for Parkinson's disease: Harnessing photothermal and phagocytosis-driven delivery of levodopa nanocarriers across the blood-brain barrier

Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB. Furthermore, levodopa metabolism generates reactive oxygen species (ROS), exacerbating neuronal damage. Systemic pulsatile dosing further disrupts natural physiological buffering mechanisms. In this investigation, we devised a ROS-responsive levodopa prodrug system capable of releasing the drug and reducing ROS levels in the central nervous system. The prodrug was incorporated within second near-infrared region (NIR-II) gold nanorods (AuNRs) and utilized angiopep-2 (ANG) for targeted delivery across the BBB. The processes of tight junction opening and endocytosis facilitated improved levodopa transport. ROS scavenging helped alleviate neuronal oxidative stress, leading to enhanced behavioral outcomes and reduced oxidative stress levels in a mouse model of PD. Following treatment, the PD mouse model exhibited enhanced flexibility, balance, and spontaneous exploratory activity. This approach successfully alleviated the motor impairments associated with the disease model. Consequently, our strategy, utilizing NIR-Ⅱ AuNRs and ANG-mediated BBB penetration, coupled with the responsive release of levodopa, offers a promising approach for dopamine supplementation and microenvironmental regulation. This system holds substantial potential as an efficient platform for delivering neuroprotective drugs and advancing PD therapy.

SlLTPg1, a tomato lipid transfer protein, positively regulates in response to biotic stresses

Late blight, caused by Phytophthora infestans (P. infestans), is among the most devastating diseases affecting tomato and other Solanaceae species. Lipid transfer proteins (LTPs) represent a class of small, basic proteins that play a crucial role in combating biotic stresses. Previous studies have shown that SlLTPg1 most strongly responds after P. infestans infestation among the LTPs family in tomato. However, the function of SlLTPg1 in disease resistance remains unclear. Here, we constructed transient overexpression and VIGS-silenced plants of SlLTPg1. Our results revealed that SlLTPg1 plays a regulatory role in enhancing tomato resistance against P. infestans. This enhancement was attributed to the upregulation of defense-related genes and reactive oxygen species (ROS) scavenging genes, as well as increased enzymatic antioxidant activities. Importantly, we found that the SlLTPg1 protein significantly inhibited the growth of Fusarium oxysporum (F. oxysporum) by observing the zone of inhibition. Interestingly, we found smaller lesion diameters and upregulated expression levels of PR genes in transient overexpression SlLTPg1 of tobacco. Therefore, we further constructed transgenic tobacco lines of SlLTPg1, presenting evidence that overexpression of SlLTPg1 could positively regulate the resistance of tobacco to F. oxysporum. These findings revealed the role of SlLTPg1 in tomato resistance to P. infestans and tobacco resistance to F. oxysporum. Moreover, we propose SlLTPg1 as a potential candidate gene for augmenting broad-spectrum plant resistance against pathogens.

Tailored small molecule for inflammation treatment: Dual scavenger targeting nitric oxide and reactive oxygen species

Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates N-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through in vitro studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases.

Microneedle-Delivered PDA@Exo for Multifaceted Osteoarthritis Treatment via PI3K-Akt-mTOR Pathway.

Osteoarthritis (OA) is marked by cartilage deterioration, subchondral bone changes, and an inflammatory microenvironment. The study introduces the Microneedle-Delivered Polydopamine-Exosome (PDA@Exo MN), a therapeutic that not only preserves cartilage and promotes bone regeneration but also improves localized drug delivery through enhanced penetration capabilities. PDA@Exo MN shows strong reactive oxygen species(ROS) scavenging abilities and high biocompatibility, fostering osteogenesis and balancing anabolic and catabolic processes in cartilage. It directs macrophage polarization from M0 to the anti-inflammatory M2 phenotype. RNA sequencing of treated chondrocytes demonstrates restored cellular function and activated antioxidant responses, with modulated inflammatory pathways. The PI3K-AKT-mTOR pathway's activation, essential for PDA@Exo's effects, is confirmed via bioinformatics and Western blot. In vivo assessments robustly validate that PDA@Exo MN prevents cartilage degradation and OA progression, supported by histological assessments and micro-CT analysis, highlighting its disease-modifying impact. The excellent biocompatibility of PDA@Exo MN, verified through histological (H&E) and blood tests showing no organ damage, underscores its safety and efficacy for OA therapy, making it a novel and multifunctional nanomedical approach in orthopedics, characterized by organ-friendliness and biosecurity.

Disruption of Poly(ADP-ribosyl)ation Improves Plant Tolerance to Methyl Viologen-Mediated Oxidative Stress via Induction of ROS Scavenging Enzymes.

ADP-ribosylation (ADPRylation) is a mechanism which post-translationally modifies proteins in eukaryotes in order to regulate a broad range of biological processes including programmed cell death, cell signaling, DNA repair, and responses to biotic and abiotic stresses. Poly(ADP-ribosyl) polymerases (PARPs) play a key role in the process of ADPRylation, which modifies target proteins by attaching ADP-ribose molecules. Here, we investigated whether and how PARP1 and PARylation modulate responses of Nicotiana benthamiana plants to methyl viologen (MV)-induced oxidative stress. It was found that the burst of reactive oxygen species (ROS), cell death, and loss of tissue viability invoked by MV in N. benthamiana leaves was significantly delayed by both the RNA silencing of the PARP1 gene and by applying the pharmacological inhibitor 3-aminobenzamide (3AB) to inhibit PARylation activity. This in turn reduced the accumulation of PARylated proteins and significantly increased the gene expression of major ROS scavenging enzymes including SOD (NbMnSOD; mitochondrial manganese SOD), CAT (NbCAT2), GR (NbGR), and APX (NbAPX5), and inhibited cell death. This mechanism may be part of a broader network that regulates plant sensitivity to oxidative stress through various genetically programmed pathways.

LrHSP17.2 Plays an Important Role in Abiotic Stress Responses by Regulating ROS Scavenging and Stress-Related Genes in Lilium regale.

As an important part of heat shock response module, heat shock proteins (HSP) play an important role in plant defense response against heat stress; however, the involvement of the majority of the HSP family members against other abiotic stresses remains poorly understood. In the present study, LrHSP17.2 was identified and its function against abiotic stress was analyzed. The expression level of LrHSP17.2 was significantly induced by heat. Heterologous transgenes of LrHSP17.2 showed that LrHSP17.2 can increase the activity of catalase, peroxidase, superoxide dismutase to removes excess reactive oxygen species (ROS), maintain the stability of the membrane structure, and regulate genes related to antioxidant enzymes and defense under abiotic stress. In addition, LrHSP17.2 could be regulated by exogenous abscisic acid and melatonin, and the related hormone synthesis genes of transgenic plants were significantly up-regulated under heat stress. Taken together, our results revealed that LrHSP17.2 is involved in regulating abiotic stress responses by regulating ROS scavenging and stress-related genes in Lilium regale.

GDSL in Lilium pumilum (LpGDSL) Confers Saline-Alkali Resistance to the Plant by Enhancing the Lignin Content and Balancing the ROS.

In order to explore the response mechanism of Lilium pumilum (L. pumilum) to saline-alkali stress, we successfully cloned LpGDSL (GDSL lipase, Gly-Asp-Ser-Leu) from L. pumilum. The qRT-PCR results indicated that the LpGDSL expression was higher in the leaves of L. pumilum, and the expression of the LpGDSL reached the highest level at 12 h in leaves under 11 mM H2O2, 200 mM NaCl, 25 mM Na2CO3, and 20 mM NaHCO3. The bacteriophage overexpressing LpGDSL was more tolerant than the control under different NaHCO3 contents. Overexpressed and wild-type plants were analyzed for phenotype, chlorophyll content, O2- content, H2O2 content, lignin content, and so on. Overexpressed plants had significantly higher resistance than the wild type and were less susceptible to saline-alkali stress. The yeast two-hybrid and BiFC assays demonstrated the existence of an interaction between LpGDSL and LpBCP. The yeast one-hybrid assay and transcriptional activation assay confirmed that B3 transcription factors could act on LpGDSL promoters. Under saline-alkali stress, L. pumilum will promote the expression of LpGDSL, which will then promotes the accumulation of lignin and the scavenging of reactive oxygen species (ROS) to reduce its damage, thus improving the saline-alkali resistance of the plant.

Cadmium exposure induces skeletal muscle insulin resistance through the reactive oxygen species-mediated PINK1/Parkin pathway

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

Profiling biomanufactured extracellular vesicles of human forebrain spheroids in a Vertical-Wheel Bioreactor.

Extracellular vesicles (EVs) secreted by human brain cells have great potential as cell-free therapies in various diseases, including stroke. However, because of the significant amount of EVs needed in preclinical and clinical trials, EV applicationis still challenging. Vertical-Wheel Bioreactors (VWBRs) have designed features that allow for scaling up the generation of human forebrain spheroid EVs under low shear stress. In this study, EV secretion by human forebrain spheroids derived from induced pluripotent stem cells as 3D aggregates and on Synthemax II microcarriers in VWBRs were investigated with static aggregate culture as a control. The spheroids were characterized by metabolite and transcriptome analysis. The isolated EVs were characterized by nanoparticle tracking analysis, electron microscopy, and Western blot. The EV cargo was analyzed using proteomics and miRNA sequencing. The in vitro functional assays of an oxygen and glucose-deprived stroke model were conducted. Proof of concept in vivo study was performed, too. Human forebrain spheroid differentiated on microcarriers showed a higher growth rate than 3D aggregates. Microcarrier culture had lower glucose consumption per million cells and lower glycolysis gene expression but higher EV biogenesis genes. EVs from the three culture conditions showed no differences in size, but the yields from high to low were microcarrier cultures, dynamic aggregates, and static aggregates. The cargo is enriched with proteins (proteomics) and miRNAs (miRNA-seq), promoting axon guidance, reducing apoptosis, scavenging reactive oxygen species, and regulating immune responses. Human forebrain spheroid EVs demonstrated the ability to improve recovery in an in vitro stroke model and in vivo. Human forebrain spheroid differentiation in VWBR significantly increased the EV yields (up to 240-750 fold) and EV biogenesis compared to static differentiation due to the dynamic microenvironment and metabolism change. The biomanufactured EVs from VWBRs have exosomal characteristics and more therapeutic cargo and are functional in in vitro assays, which paves the way for future in vivo stroke studies.

PlPOD45 positively regulates high-temperature tolerance of herbaceous peony by scavenging reactive oxygen species.

The online version contains supplementary material available at 10.1007/s12298-024-01505-x.

Integrated transcriptomic and proteomic analysis unravels the response mechanisms of Saccharina japonica to heat stress

High temperature is a major abiotic stress that limits the growth and productivity of seaweed. Over the past decades, the cold-temperate seaweed Saccharina japonica has been domesticated and gradually adapted to subtropical regions with higher temperatures. However, there is limited knowledge regarding the molecular responses of S. japonica to heat stress. In this study, an integrated transcriptomic and proteomic analysis was performed to explore the molecular mechanism underlying the response to heat stress in S. japonica. A total of 6777 genes and 226 proteins were identified that exhibited differential expression in heat stress samples comparison to non-stress sample. GO analysis revealed that the GO molecular function (MF) terms related to unfolded protein binding/protein binding, and heat shock protein (HSP) binding/HSP90 binding were significantly enriched in the up-regulated DEGs/DEPs in S. japonica sporophytes under heat stress. Further analysis of the global gene and protein expression profiles unveiled the potential mechanisms in S. japonica to alleviate heat stress through up-regulation of the heat stress transcription factor-heat shock proteins-HSP70/HSP90 organising proteins (HSF-HSPs-HOPs) module, down-regulation of reactive oxygen species (ROS) generation and up-regulation of ROS scavenging. Our results provide novel insights into the heat stress acclimation mechanism in S. japonica, and would benefit future selection of heat-tolerant varieties.

Elucidating the Role of SlBBX31 in Plant Growth and Heat-Stress Resistance in Tomato.

Heat stress inhibits plant growth and productivity. Among the main regulators, B-box zinc-finger (BBX) proteins are well-known for their contribution to plant photomorphogenesis and responses to abiotic stress. Our research pinpoints that SlBBX31, a BBX protein harboring a conserved B-box domain, serves as a suppressor of plant growth and heat tolerance in tomato (Solanum lycopersicum L.). Overexpressing (OE) SlBBX31 in tomato exhibited yellowing leaves due to notable reduction in chlorophyll content and net photosynthetic rate (Pn). Furthermore, the pollen viability of OE lines obviously decreased and fruit bearing was delayed. This not only affected the fruit setting rate and the number of plump seeds but also influenced the size of the fruit. These results indicate that SlBBX31 may be involved in the growth process of tomato, specifically in terms of photosynthesis, flowering, and the fruiting process. Conversely, under heat-stress treatment, SlBBX31 knockout (KO) plants displayed superior heat tolerance, evidenced by their improved membrane stability, heightened antioxidant enzyme activities, and reduced accumulation of reactive oxygen species (ROS). Further transcriptome analysis between OE lines and KO lines under heat stress revealed the impact of SlBBX31 on the expression of genes linked to photosynthesis, heat-stress signaling, ROS scavenging, and hormone regulation. These findings underscore the essential role of SlBBX31 in regulating tomato growth and heat-stress resistance and will provide valuable insights for improving heat-tolerant tomato varieties.

Nanobiotechnology-mediated regulation of reactive oxygen species homeostasis under heat and drought stress in plants.

Global warming causes heat and drought stress in plants, which affects crop production. In addition to osmotic stress and protein inactivation, reactive oxygen species (ROS) overaccumulation under heat and drought stress is a secondary stress that further impairs plant performance. Chloroplasts, mitochondria, peroxisomes, and apoplasts are the main ROS generation sites in heat- and drought-stressed plants. In this review, we summarize ROS generation and scavenging in heat- and drought-stressed plants and highlight the potential applications of plant nanobiotechnology for enhancing plant tolerance to these stresses.

Dual-Level Reactive Oxygen Species Amplifier for Enhanced Photothermal-Chemodynamic Therapy.

Chemodynamic therapy is an appealing modality in cancer treatment. However, its therapeutic effectiveness is impeded by insufficient catalytic efficiency and overexpression of glutathione (GSH) at the tumor site. In this study, a poly(o-phenylenediamine) (PoPD)@copper sulfide (CuS) nanoplatform was developed as dual-level reactive oxygen species (ROS) amplifier for enhanced photothermal-chemodynamic therapy. The PoPD@CuS nanoplatform exhibited photothermal performance, chemodynamic performance, and GSH-depleting capability. Alongside its improved photothermal conversion efficiency with tumor pH-responsiveness, the photothermal behavior of PoPD@CuS could elevate chemodynamic activity by regulating the temperature spatiotemporally, leading to increased ROS production. Moreover, GSH depletion of PoPD@CuS could suppress ROS scavenging, further enhancing oxidative stress in the tumor region. Consequently, functioning as a dual-level ROS amplifier, PoPD@CuS showcased remarkable effectiveness in photothermal-chemodynamic combination therapy.

Multifunctional polymeric nanocapsules with enhanced cartilage penetration and retention for osteoarthritis treatment

Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and subchondral bone homeostasis imbalance. Effective topical OA therapy is challenging, as therapeutic drugs often suffer from insufficient penetration and rapid clearance. We develop miniature polydopamine (PDA) nanocapsules (sub-60 nm), which are conjugated with collagen-binding polypeptide (CBP) and loaded with an anabolic drug (i.e., parathyroid hormone 1–34, PTH 1–34) for efficient OA treatment. Such multifunctional polymeric nanocapsules, denoted as PDA@CBP-PTH, possess deformability when interacting with the dense collagen fiber networks, enabling the efficient penetration into 1 mm cartilage in 4 h and prolonged retention within the joints up to 28 days. Moreover, PDA@CBP-PTH nanocapsules exhibit excellent reactive oxygen species scavenging property in chondrocytes and enhance the anabolism in subchondral bone. The nanosystem, as dual-mode treatment for OA, demonstrates rapid penetration, long-lasting effects, and combinational therapeutic impact, paving the way for reversing the progression of OA for joint health care.