Release Of Reactive Oxygen Species Research Articles

ROS-regulated SUR1-TRPM4 drives persistent activation of NLRP3 inflammasome in microglia after whole-brain radiation

Delayed radiation-induced brain injury (RIBI) characterized by progressive cognitive decline significantly impacts patient outcomes after radiotherapy. The activation of NLRP3 inflammasome within microglia after brain radiation is involved in the progression of RIBI by mediating inflammatory responses. We have previously shown that sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) mediates microglial NLRP3-related inflammation following global brain ischemia. However, the role of SUR1-TRPM4 in RIBI remains unclear. Here, we found that whole-brain radiation induced up-regulation and assembly of SUR1-TRPM4, which further activated the NLRP3 inflammasome in microglia and caused persistent neuroinflammation in mice. Blocking SUR1-TRPM4 by glibenclamide or gene deletion of Trpm4 effectively prevented NLRP3-mediated neuroinflammation and alleviated RIBI. Utilizing the mouse model of RIBI and irradiated BV2 cells, we further demonstrated that irradiation caused mitochondrial damage to microglia, leading to violent release of reactive oxygen species (ROS), which enhanced the transcription of SUR1, TRPM4, and NLRP3 inflammasome-related molecules. Moreover, ROS up-regulated ten-eleven translocation 2 (TET2) to enhance TRPM4 expression by mediating the demethylation of the gene promoter, thereby facilitating the assembly of SUR1-TRPM4 in microglia. In summary, this study deciphers that SUR1-TRPM4 crucially mediates the persistent activation of microglial NLRP3 inflammasome under the action of ROS after whole-brain radiation, offering novel therapeutic strategies for delayed RIBI as well as other NLRP3-related neurological disorders involving excessive ROS production.

Nanoparticles containing intracellular proteins modulate neutrophil functional and phenotypic heterogeneity

Neutrophils are rapidly recruited to sites of infection, injury, or to immune complexes. Upon arrival, they initiate degranulation, release reactive oxygen species (ROS), and/or nuclear extracellular traps (NETs) to eliminate invading microorganisms, clear debris, or remove abnormal immunoglobulins. While these processes ideally trigger healing and a return to balance, overshooting neutrophil function can lead to life-threatening infections such as sepsis or persistent inflammation observed in various autoimmune diseases. However, recent evidence highlights a phenotypic and functional heterogeneity of neutrophils that extends well beyond their traditional - potentially harmful- role as first responders. For example, neutrophils regulate ongoing inflammation by modulating macrophage function through efferocytosis, T cell responses by antigen presentation and the release of cytokines. The factors that induce neutrophil differentiation into activating or regulatory phenotypes remain poorly defined. Here, we hypothesize that intracellular components that have been released into the extracellular space could contribute to the phenotypic heterogeneity of neutrophils. To find out, we used nanoparticles composed of intracellular proteins (cell-derived nanoparticles, CDNPs) and analyzed their effects on cultured murine bone marrow neutrophils (BMN). We observed that CDNPs activate BMN transiently with an increase in the expression of CD11b without triggering classical effector functions. Additionally, CDNPs induce the secretion of IL-10, shift PMA-induced cell death toward apoptosis, and increase the expression of CD80. Mechanistically, our findings indicate that 26% of BMNs ingest CDNPs. These BMNs preferentially express CD54+, fail to migrate toward CXCL12, exhibit diminished responses to LPS, and undergo apoptosis. These data identify CDNPs as biomaterials that modulate neutrophil behavior by fine-tuning the expression of CD11b and CD80.

Extraction, purification, structural characterization, and anti-inflammatory activity of a polysaccharide from Lespedeza formosa.

A new acidic polysaccharide was extracted from Lespedeza Formosa (LF) using microwave-assisted extraction. After a progressive purification, Lespedeza Formosa polysaccharide (LFP-1) with 96.14 % purity and moderate molecular weight was obtained. Subsequently, LFP-1's structural analysis and in vitro anti-inflammatory experiments were performed. LFP-1 is composed of nine monosaccharides, mainly including 39.7 % glucose, 29.1 % galactose, and 19.9 % arabinose, with three branched chains of its structure. The diverse monosaccharides and branched chains provided the essential conditions for the anti-inflammatory effects of LFP-1, which diminished the release of nitric oxide (NO) and reactive oxygen species (ROS). And they altered the release of internal inflammatory factors in lipopolysaccharide (LPS)-treated macrophages. LFP-1 exerted intracellularly anti-inflammatory effects through the nuclear factor kappa-B (NF-κB) signal pathway. The discovery of LFP-1 opens up a new possibility for natural anti-inflammatory medicine.

The impact of obesity on mitochondrial dysfunction during pregnancy.

Mitochondria play a central role in nutrient metabolism, besides being responsible for the production of adenosine triphosphate (ATP), the main source of cellular energy. However, the ATP production process is associated with the generation of reactive oxygen species (ROS), which excessive accumulation can cause mitochondrial dysfunction. This dysfunction, in turn, causes the accumulation of fatty acids in the adipose tissue, triggering a local inflammatory process that can evolve into systemic inflammation. In women with obesity, an increase in lipid levels in the placental environment is observed. The high presence of fatty acids compromises the structural integrity and mitochondrial membrane, culminating in the release of ROS. This process damages the DNA of placental cells and causes an inflammatory state, affecting metabolic efficiency. This vicious cycle is characterized by defects in mitochondrial ATP production, which can lead to lipid accumulation and inflammation. In pregnant women with obesity, these mitochondrial changes play a determining role in pregnancy outcomes. Hence, the objective of this study was to search the literature to review the impact of mitochondrial dysfunction in the maternal obesity.

The Anti‐Inflammatory Activities of Sphagnum palustre L. Ethanol Extract to Control Inflammation in RAW264.7 Cells

ABSTRACTDiscomfort caused by inflammation leads to stress and anxiety in patients and seriously decreases the patients' quality of life. People prefer to use natural products instead of anti‐inflammatory drugs because of their low toxicity and side effects. Studies have shown that Sphagnum palustre L. (S. palustre) can be used as medicinal plant, but few studies have focused on its anti‐inflammatory effects. This study explored the mechanism of action of the ethanol extract of the peat moss plant S. palustre on lipopolysaccharide‐induced inflammation in macrophage RAW264.7 cells. Components in S. palustre ethanol extracts (SPE) were identified by HPLC‐MS, which mainly included 4‐methoxybenzaldehyde, 4‐methoxycinnamaldehyde and oleanolic acid. The effects of different concentrations (6.25–100 μg/mL) of SPE after 24 h administration were evaluated to establish a cellular inflammation model. Three biological replicates were performed based on each experiment, the MTT assay results showed that a low concentration of SPE promoted cell proliferation marked by Formazan. In a neutral red uptake assay, the SPE group was effectively inhibited the cell phagocytosis rate. With the increase of SPE concentration, intracellular ROS release decreased, which detected by DCFH‐DA. Immunofluorescence assay result showed that SPE inhibited the release of reactive oxygen species from macrophages with fluorescent markers and DAPI. SPE inhibited the release of nitric oxide from macrophages as well. What's more, SPE significantly decreased the protein expression of interleukin (IL)‐1, IL‐6, and nuclear factor (NF)‐κB according to enzyme‐linked immunosorbent and immunocytochemical assays. SPE reduces inflammation in macrophage RAW264.7 cells and thus is a promising natural anti‐inflammatory plant.

4-O-Methylglucuronoxylan from Hygrophila Ringens var. Ringens Seeds: Chemical Composition and Anti-Inflammatory Activity.

Hygrophila ringens var. ringens is a medicinal plant of the Acanthaceae family. A soluble polysaccharide is extracted from H. ringens seeds using warm water, followed by deproteinization and purification using column chromatography. DL1 is characterized comprehensively using spectroscopic and chromatographic techniques and identified as a polymer containing xylose (Xyl; 78.5%) and 4-O-methyl-d-glucuronic acid (4-O-MeGlcA; 21.5 %). The most prominent glycosidic linkages detected are terminal-xylose (T-Xyl); 1,2,3,4-Xylp; 1,2,4-Xylp; and T-4-O-MeGlcA. DL1 belongs to the xylan group and is a 4-O-methylglucuronoxylan. DL1 exhibits inhibition of bovine serum albumin denaturation with IC50 values of 0.35mgmL-1 and a similar activity to diclofenac (non-steroidal anti-inflammatory drug). In a model of lipopolysaccharide-stimulated macrophages, DL1 (20-40µgmL-1) strongly inhibits inflammatory cytokines and reactive oxygen species release without having significant macrophage cytotoxicity. The inhibitory effect of DL1 on inflammatory cytokines is mediated by the activation of mitogen-activated protein kinases by inhibiting the phosphorylation of p38 and extracellular signal-regulated kinase. These results highlight the potential of DL1 for treating inflammation through its cytokine-suppressive activity.

Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) -DNA-based structures with cytotoxic proteins-that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly-without systemic absorption-could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.

Monocytic reactive oxygen species-induced T cell apoptosis impairs cellular immune response to SARS-CoV-2 mRNA vaccine.

We have recently shown that, during acute severe COVID-19, SARS-CoV-2 spike protein (S) induces a cascade of events resulting in T cell apoptosis. Indeed, by neutralizing the protease activity of its receptor, ACE2, S induces an increase in circulating Angiotensin II (AngII), resulting in monocytic release of reactive oxygen species (ROS) and programmed T cell death. Here, we tested whether SARS-CoV-2 mRNA vaccines, known to cause the circulation of the vaccine antigen, S-protein receptor binding domain (RBD), might trigger the same cascade. To this aim, we used ELISA to quantify the presence of RBD and AngII in participants' peripheral blood as well as the presence of interferon-γ in the supernatant of peripheral blood mononuclear cells (PBMCs) exposed to S. Monocytic ROS production, T cell apoptosis, and S-induced T lymphocyte proliferation were measured by flow cytometry, and DNA damage by immunofluorescence. In most vaccinees, we observed the presence of circulating RBD peaking on Day 14, and linked to an increase in AngII plasma levels with a peak on Day 28. This increase correlated with i) the ability of monocytes to produce ROS and to induce ROS-mediated DNA damage in neighboring cells, including PBMCs, ii) CD4+ and CD8+ T lymphocyte apoptosis, and iii) a poor response to S in vitro from both CD4+ and CD8+ T cells. We observed the same cascade of events triggered by the vaccinal antigen as by SARS-CoV-2 infection. This cascade may account for the suboptimal efficiency of mRNA SARS-CoV-2 vaccines in preventing the infection, the limited vaccine memory, and certain side-effects. In this model, AngII receptor antagonists and/or antioxidants might improve the performance of the SARS-CoV-2 vaccine.

Regulation of calcium homeostasis in endoplasmic reticulum–mitochondria crosstalk: implications for skeletal muscle atrophy

This review comprehensively explores the critical role of calcium as an essential small-molecule biomessenger in skeletal muscle function. Calcium is vital for both regulating muscle excitation–contraction coupling and for the development, maintenance, and regeneration of muscle cells. The orchestrated release of calcium from the endoplasmic reticulum (ER) is mediated by receptors such as the ryanodine receptor (RYR) and inositol 1,4,5-trisphosphate receptor (IP3R), which is crucial for skeletal muscle contraction. The sarcoendoplasmic reticulum calcium ATPase (SERCA) pump plays a key role in recapturing calcium, enabling the muscle to return to a relaxed state. A pivotal aspect of calcium homeostasis involves the dynamic interaction between mitochondria and the ER. This interaction includes local calcium signaling facilitated by RYRs and a “quasi-synaptic” mechanism formed by the IP3R-Grp75-VDAC/MCU axis, allowing rapid calcium uptake by mitochondria with minimal interference at the cytoplasmic level. Disruption of calcium transport can lead to mitochondrial calcium overload, triggering the opening of the mitochondrial permeability transition pore and subsequent release of reactive oxygen species and cytochrome C, ultimately resulting in muscle damage and atrophy. This review explores the complex relationship between the ER and mitochondria and how these organelles regulate calcium levels in skeletal muscle, aiming to provide valuable perspectives for future research on the pathogenesis of muscle diseases and the development of prevention strategies.

Sea Anemone Kunitz Peptide HCIQ2c1 Reduces Histamine-, Lipopolysaccharide-, and Carrageenan-Induced Inflammation via the Suppression of Pro-Inflammatory Mediators

Inflammation is a physiological response of the immune system to infectious agents or tissue injury, which involves a cascade of vascular and cellular events and the activation of biochemical pathways depending on the type of harmful agent and the stimulus generated. The Kunitz peptide HCIQ2c1 of sea anemone Heteractis magnifica is a strong protease inhibitor and exhibits neuroprotective and analgesic activities. In this study, we investigated the anti-inflammatory potential of HCIQ2c1 in histamine- and lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as well as in LPS-induced systemic inflammation and carrageenan-induced paw edema models in CD-1 mice. We found that 10 μM HCIQ2c1 dramatically decreases histamine-induced intracellular Ca2+ release and LPS-induced reactive oxygen species (ROS) production in RAW 264.7 macrophages. Moreover, HCIQ2c1 significantly inhibited the production of LPS-induced tumor necrosis factor α (TNF-α), inducible NO-synthase (iNOS), and 5-lipoxygenase (5-LO) but slightly influenced the IL-1β and cyclooxygenase-2 (COX-2) expression level in macrophages. Furthermore, intravenous administration by HCIQ2c1 at 0.1 mg/kg dose reduced LPS-induced TNF-α, IL-1β, COX-2, and iNOS gene expression in CD-1 mice. The subplantar administration of HCIQ2c1 at 0.1 mg/kg dose to mice significantly reduced carrageenan-induced paw edema by a factor of two, which is comparable to the effect of diclofenac at 1 mg/kg dose. Thus, peptide HCIQ2c1 has a strong anti-inflammatory potential by the attenuation of systemic and local inflammatory effects through the inhibition of intracellular Ca2+ release, the production of ROS and pro-inflammatory cytokines, and enzymes involved in arachidonic acid metabolism.

Acid-responsive singlet oxygen nanodepots.

The singlet oxygen carrier addresses the challenges of traditional photodynamic therapy (PDT), which relies on the presence of oxygen within solid tumors and struggles with light penetration issues. However, the inability to control the release of singlet oxygen has hindered precise treatment applications. Here, we introduce an acid-responsive singlet oxygen nanodepot (aSOND) designed to overcome this limitation. The aSOND is synthesized using a responsive diblock copolymer system that includes a hydrophilic PEG block and a pH-responsive block with singlet oxygen loading sites. In neutral or alkaline environments, the aSOND releases singlet oxygen slowly, ensuring stability in blood circulation. In contrast, in acidic environments such as the tumor microenvironment or intracellular lysosomes, protonation of the tertiary amine group within the pH responsive block increases the hydration of the polymer, triggering a rapid release of singlet oxygen. This feature enables controlled, tumor-specific release of reactive oxygen species (ROS). The aSOND system effectively implements an "OFF-ON" singlet oxygen therapy, demonstrating high spatiotemporal selectivity and independence from both oxygen supply and external light, offering a promising approach for targeted cancer therapy.

NETs exacerbate placental inflammation and injury through high mobility group protein B1 during preeclampsia.

Inflammatory stress at the maternal-fetal interface plays an important role in the occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) at the maternal-fetal interface are believed to be among the main pathogenic factors leading to preeclampsia and the worsening of its symptoms. However, the underlying mechanism is largely unclear. This study aimed to elucidate the role of high mobility group box 1 (HMGB1) in NETs involved in the pathogenesis of PE. The concentration of NETs was detected in the plasma of patients with PE using enzyme-linked immunosorbent assay (ELISA). Placental samples were collected from patients with PE to detect the expression of HMGB1 through Western Blot and PCR. For in vitro experiments, human trophoblast HTR-8/SVneo cells were treated with NETs, and their proliferation, invasion, migration, and apoptosis ability; degree of oxidative stress; and secretion of inflammatory factors were detected. Compared with that in normal pregnant women, an increase in the release of NETs was observed in the peripheral blood of patients with PE. HMGB1 was increased in the placenta of PE patients and colocalized with NETs. The treatment of human trophoblast HTR-8/SVneo cells with NETs resulted in the inhibition of HTR-8/SVneo cell invasion and migration and increases in the release of reactive oxygen species (ROS), and several inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α). These damaging effects can be reversed by the HMGB1 scavenger glycyrrhizin, which indicates that NETs can mediate trophoblast damage and the expression of several inflammatory factors through HMGB1. NETs can cause trophoblast inflammation-related functional damage through HMGB1 during the occurrence and development of preeclampsia. HMGB1 produces a marked effect in the PE cascade of oxidative stress involving NETs. Inhibiting HMGB1 to suppress NETs damage is a possible approach for the future treatment of PE.

A versatile two light mode triggered system for highly localized sequential release of reactive oxygen species and conjugated drugs from mesoporous organosilica particles

The increasing prevalence of antimicrobial resistance and adverse effects from systemic treatments calls for urgent reevaluation of current methods that rely on excessive, uncontrolled drug administration. In recent years triggerable...

The Role of Microglia in Parkinson's Disease and Possible Therapeutic Targets

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor and non-motor symptoms. Recent research highlights the critical role of microglia, the resident immune cells of the central nervous system, in the pathogenesis and progression of PD. Microglia contribute to neuroinflammation through the release of pro-inflammatory cytokines and reactive oxygen species, exacerbating neuronal damage. Moreover, α-synuclein aggregates, a hallmark of PD, activate microglia, further promoting inflammation and neurodegeneration. This review explores the dual role of microglia in PD, encompassing both their neuroprotective functions and their contribution to neuroinflammation. We discuss the molecular mechanisms underlying microglial activation and their interactions with astrocytes, another crucial glial cell type. The review also examines potential therapeutic targets aimed at modulating microglial activity to mitigate neuroinflammation and slow the progression of PD. Current therapeutic strategies predominantly focus on symptomatic relief through dopaminergic medications. However, emerging therapies targeting microglial activation, such as anti-inflammatory drugs, immunomodulators, and novel agents like metabotropic glutamate receptor 5 (mGluR5) modulators, offer promising avenues for disease modification. Understanding the complex interplay between microglia and other cellular components in the PD brain is essential for developing effective treatments that address the underlying pathophysiological mechanisms of the disease.

The immunomodulatory potential of chickpea protein hydrolysate via ROS and NO pathways.

The uncontrolled overproduction of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) is linked to chronic inflammation, although they are also essential signaling molecules for the immune system against infectious agents. Bioactive compounds hold promise as functional bioactive nutrients, contributing to the immunomodulatory response. This study investigates the potential of chickpea protein hydrolysate to modulate ROS/RNS stress and inflammatory responses in a cellular low-grade chronic inflammatory model. This study was focused on their effects on endogenous antioxidant enzyme activities and key pro-inflammatory markers. ROS and nitric oxide (NO) production and molecular biology techniques were used to evaluate cell metabolism. Hydrolysate exposure notably increased ROS and NO release in a dose-dependent manner, while also exhibiting significant anti-inflammatory effects by inhibiting NF-κB and NLRP3 inflammasome components in treated cells. Therefore, chickpea protein hydrolysates hold promise as functional bioactive compounds for use in therapeutic applications, promoting human health and well-being.

Effect and mechanism of oritavancin on hIAPP amyloid formation.

Amyloidosis of the human islet amyloid polypeptide (hIAPP) is closely related to the pathogenesis of type 2 diabetes (T2D) and serves as both a diagnostic hallmark and a key therapeutic target for T2D. In this study, we discovered that oritavancin (Ori), a glycopeptide antibiotic primarily prescribed for Gram-positive bacterial infections, can dose-dependently inhibit recombinant hIAPP (rhIAPP) amyloid formation. Ori specifically inhibited rhIAPP amyloid formation at the initial nucleation stage but didn't affect mature rhIAPP fibrils. As a result, Ori reduced amyloidosis of rhIAPP induced pancreatic NIT-1 cell apoptosis and reactive oxygen species (ROS) release. Based on the results from studies involving antibiotic homologues of Ori and its acid hydrolysates, we demonstrated that both the N-(4-chlorobiphenyl) methyl group (CBP) and glycopeptide backbone were necessary for inhibiting rhIAPP amyloid formation. The mechanism behind Ori on rhIAPP amyloid formation lies in the direct interaction of the two molecules identified by ESI-MS and molecular docking assays. Consequently, this research not only lays the groundwork for developing novel therapeutic approaches for T2D but also presents the opportunity to repurpose Ori as a treatment option.

PsDMAP1/PsTIP60-regulated H4K16ac is required for ROS-dependent virulence adaptation of Phytophthora sojae on host plants

Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete Phytophthora sojae manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress. Mechanistically, the P. sojae DNA methyltransferase 1-associated protein (PsDMAP1) binds Tat-interactive protein 60 (PsTIP60) to comediate histone H4 acetylation on lysine 16 (H4K16ac). This regulation affects RNA polymerase II (pol II) recruitment, transcriptional induction of DDR-related genes, and the enrichment of histone H2Ax phosphorylated on serine 137 (γH2Ax) in response to both plant immunity and fungicide stress. The resulting H4K16ac serves as a crucial transgenerational epigenetic signal for virulence adaptation of P. sojae on plants, as a result of adaptation to ROS stress.

The anticarcinogenic properties of manuka honey - a literature review

Background: Since antiquity, honey has been recognised for its healing and antibacterial properties. Recently, Manuka honey (MH) has been identified as possessing antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic effects. Objective: This review examines the potential benefits of manuka honey, its bioactive components, and their effects on cancerogenesis, cancer growth, and development. Methods: The PubMed and Google Scholar databases were searched, and 46 studies were identified as most relevant to the research objective. Results: The accompanying papers posit that MH may impede carcinogenesis by regulating various molecular pathways and cancer cell progression. A substantial body of scientific evidence indicates that a range of honey types, including MH, can facilitate the release of reactive oxygen species and cytokines (predominantly IL-1β, IL-6, and TNF-α) by innate immune system cells. Furthermore, studies have demonstrated that honey can stimulate T lymphocytes and macrophages' proliferation and functions while also inducing apoptosis and cell cycle arrest in cancer cells. Conclusion: The body of evidence attesting to the anticarcinogenic properties of MH continues to grow. Several studies have demonstrated the significant role of manuka honey and its properties in promoting innate and adaptive immunity, which is essential for eliminating cancer cells. Nevertheless, further research is required to provide comprehensive data regarding the active constituents of Manuka honey and their potential efficacy in cancer therapy.

Does Encapsulation of π‐Conjugated Polymer Nanoparticles within Biodegradable PEG–PLGA Matrices Mitigate Photoinduced Free Radical Production and Phototoxicity?

AbstractLipophilic π‐conjugated polymers (CPs) encapsulated within self‐assembling diblock copolymer poly(ethylene glycol) methyl ether‐block‐poly(lactide‐co‐glycolide) (PEG–PLGA) nanoparticles, are interesting candidates for photodynamic and photothermal therapies. Upon irradiation, CPs generate reactive oxygen species (ROS), which may either cause local phototoxicity or could be exploited for photodynamic therapy. The propensity of the PEG–PLGA matrix to scavenge ROS has never been investigated. Here the ability of two PEG–PLGA structures (PEG2 kDa–PLGA4.5 kDa vs PEG5 kDa–PLGA55 kDa) to mitigate the release of ROS generated by four different CPs (PFO, F8BT, CN‐PPV, and PCPDTBT) following irradiation (5 J cm−2) at 385, 455, and 656 nm is studied. The molar content of the PEG–PLGA matrix, rather than the molecular weight or composition, appeared to be the most influential factor, i.e., lower molar concentrations of the matrix polymer are associated with significant increases in phototoxicity. Multivariate analysis reveals that the combination of CP photophysical properties and nanoparticle matrix properties are important for understanding CP nanoparticle‐induced phototoxicity.

Ginsenoside Rd-Loaded Antioxidant Polymersomes to Regulate Mitochondrial Homeostasis for Bone Defect Healing in Periodontitis.

Periodontitis is the leading cause of tooth loss in adults. Initially triggered by bacterial infection, it is characterized by subsequent dysregulation of mitochondrial homeostasis, leading to ongoing loss of periodontal tissue. Mitophagic flux, a critical physiological mechanism for maintaining mitochondrial homeostasis, is compromised in periodontitis. Additionally, increased release of reactive oxygen species (ROS) exacerbates mitochondrial damage. In this study, a ginsenoside Rd (Rd)-loaded antioxidative polymersome (RdAP) is designed, which is self-assembled from a mitochondrial-protective and ROS-scavenging block copolymer, poly(ethylene oxide)-block-poly(phenylboronic acid pinacol ester-conjugated polylysine) (PEO113-b-P(Lys-PAPE)60). The phenylboronic acid pinacol ester (PAPE) segment exhibits excellent ROS-responsive properties, enabling effective ROS scavenging through antioxidant production. Rd significantly enhances mitophagic flux by 2.5-fold in periodontal ligament stem cells (PDLSCs) under oxidative stress. Together with the antioxidative polymersome, RdAPs restore mitochondrial homeostasis and enhance the osteogenic capacity of PDLSCs, bringing it closer to that of healthy controls. In a mouse model of periodontitis, the bone mass in the RdAP-treated group is 1.37 times greater than that in the untreated periodontitis group. Overall, the findings propose a novel strategy for addressing refractory periodontitis, which may also be applicable to other diseases characterized by mitochondrial homeostasis imbalance.