Aug 2026· Bioactive Materials· Vol 67, pp. 252 - 265· 0 citations· 52 references
Medicine
TL;DR
A cerium-doped rosmarinic acid nanosystem formed via self-polymerization that catalytically eliminates ROS while simultaneously generating oxygen to reprogram the pathological renal microenvironment is reported, offering a promising strategy for precision therapy of AKI.
Abstract
Acute kidney injury (AKI) is driven by a vicious interplay among excessive reactive oxygen species (ROS) accumulation and persistent renal hypoxia, which collectively disrupt redox homeostasis and exacerbate tubular injury. However, current therapeutic strategies primarily provide supportive care and fail to simultaneously modulate these interconnected pathological stressors. Herein, we report a cerium-doped rosmarinic acid nanosystem (RA/Ce NPs) formed via self-polymerization that catalytically eliminates ROS while simultaneously generating oxygen to reprogram the pathological renal microenvironment. The ultrasmall RA/Ce NPs enable efficient chelator-free 89Zr radiolabeling for positron emission tomography (PET) imaging. Redox-switchable Ce3+/Ce4+ centers confer robust catalytic activity and ROS-responsive biodegradation, ensuring potent antioxidation with safe clearance. RA/Ce NPs suppress intracellular ROS, preserve mitochondrial membrane potential, and protect against oxidative injury in vitro. In rhabdomyolysis-induced AKI mice, PET imaging reveals pronounced renal accumulation, while treatment markedly alleviates tubular damage, oxidative stress and hypoxia, leading to restored renal function with excellent biocompatibility. This work presents a natural-product-derived catalytic nanoplatform integrating antioxidation, oxygenation, imaging and biodegradability, offering a promising strategy for precision therapy of AKI.
Cerium molybdate-doped polyaniline nanoparticles are developed to enable a synergistic combination of photothermal therapy (PTT) and CDT, thereby triggering immunogenic cell death (ICD) and enhancing antitumor immunity and presenting a robust nanoplatform integrating chemodynamic and photothermal therapies for potent cancer immunotherapy.
Yulin Kuang, Cheng Lu, Bolan Yu et al.· Bioactive Materials· 0 citations
Acute kidney injury (AKI) is a prevalent clinical syndrome associated with high morbidity, mortality, and a heavy medical burden. Oxidative stress, inflammation, and ferroptosis are key drivers of AKI, yet current pharmacotherapies are limited by suboptimal efficacy and systemic side effects. An efficient and precise kidney-targeted delivery system that co-delivers complementary therapeutics could overcome these challenges. Herein, we report a platelet membrane-coated, reactive oxygen species (ROS)-responsive nanozyme (BAPCs@PM) for synergistic AKI therapy. Ultrasmall CeO2 nanodots (~3 nm) were in situ mineralized on the outer layer of polydopamine cores, and hydrophobic baicalein was loaded into the mesoporous interior, yielding a stable and well-dispersed multifunctional composite nanozyme. Platelet membrane cloaking conferred renal targeting, immune evasion, and prolonged circulation. BAPCs@PM enabled ROS-triggered release of CeO2 nanodots and sustained baicalein delivery at injured sites, amplifying local antioxidant, anti-inflammatory, and anti-ferroptotic activity. In a cisplatin-induced AKI model, BAPCs@PM markedly suppressed kidney injury molecule-1 upregulation, inhibited cleaved caspase-3 activation and apoptosis, enhanced mitochondrial protection, modulated macrophage polarization, reduced proinflammatory cytokine production, regulated iron homeostasis, restored glutathione peroxidase 4 expression, attenuated ferroptosis and lipid peroxidation, and ultimately improved renal function. Owing to their ultrasmall size, the ceria nanodots achieved efficient renal accumulation and rapid clearance with minimal systemic toxicity. This study provides an innovative biomimetic and responsive therapeutic strategy for AKI by combining ultrasmall nanozymes, natural bioactive molecules, and biomimetic membrane engineering.
Dongjing Wang, Xiaonan Li, Kunpeng Wei et al.· Journal of Controlled Releas...· 0 citations
Acetaminophen (APAP) overdose is the leading cause of acute liver failure worldwide, yet existing therapy relies solely on N-acetylcysteine (NAC), whose efficacy diminishes markedly beyond an 8-10 h therapeutic window. The underlying pathology involves a self-amplifying cycle of reactive oxygen species (ROS) overproduction and macrophage-mediated inflammation, and strategies that concurrently scavenge ROS, reprogram macrophage polarization, and attenuate hepatocyte apoptosis remain lacking. Itaconate (ITA), an endogenous anti-inflammatory metabolite, suffers from poor membrane permeability and lacks intrinsic ROS-scavenging capacity. Herein, we constructed BiOCl@ITA by integrating defect-engineered bismuth oxychloride (BiOCl) with surface-loaded ITA. Oxygen vacancy engineering confers intrinsic superoxide dismutase (SOD)- and catalase (CAT)-mimicking activities under stimulus-free conditions. BiOCl@ITA showed rapid accumulation in the liver within 0.5 h after intraperitoneal administration and was efficiently internalized by both hepatocytes and macrophages in vitro. Moreover, BiOCl@ITA virtually eliminated intracellular ROS and attenuated APAP-induced hepatocyte injury, while also reprogramming LPS-stimulated macrophages from M1 toward an M2 phenotype, consistently outperforming free ITA across all endpoints. In a murine APAP-induced ALI model, BiOCl@ITA-treated mice showed near-complete thermal recovery by 24 h, accompanied by substantially reduced serum hepatic injury markers and attenuated histopathological damage. Hepatic molecular and tissue-level analyses further demonstrated restoration of antioxidant defenses, favorable regulation of BAX/BCL-2 expression, and sustained M1-to-M2 macrophage polarization in vivo. These findings demonstrate that BiOCl@ITA synergistically integrates catalytic ROS detoxification with ITA-mediated macrophage reprogramming, offering a promising therapeutic approach for APAP-induced acute liver injury.
Junli Huang, Huan Huang, Ke Huang et al.· ACS Applied Materials and In...· 0 citations
The persistent rise in case incidence and the acute shortage of effective treatments have heightened the urgent need for robust strategies to combat acute liver injury (ALI). Targeting reactive oxygen species (ROS) scavenging remains the predominant therapeutic approach. However, current clinical interventions and emerging therapies primarily emphasize symptomatic-level ROS elimination while neglecting endogenous ROS production inhibition, which severely limits their therapeutic efficiency. Herein, we introduce a cross-linked diselenide nanovesicles with surface folic acid modification (FA@cSeLAV), which effectively targets hepatic macrophages, key mediators of ROS-driven damage in ALI, and seamlessly integrates symptomatic-level ROS elimination with the inhibition of endogenous ROS production. Briefly, diselenide-enriched FA@cSeLAV efficiently scavenges excessive ROS and undergoes depolymerization to predominantly form the oxidized monomer selenolipoic acid (DSeO2LA). Seamlessly, DSeO2LA impairs the mitochondrial tricarboxylic acid (TCA) cycle by inhibiting the acyl group transfer activity of key mitochondrial metabolic enzymes, thus interfering with mitochondrial energy metabolism and suppressing aberrant ROS production. Impressively, this internal-external synergistic strategy maintains sustained and robust ROS regulation at normal levels within the hepatic environment, significantly surpassing the anti-inflammatory efficiency of approved drug N-acetylcysteine (NAC), offering insights for the clinical treatment of inflammation-associated diseases.
Shaoxiong Zhang, Donglin Wang, Qian Liu et al.· ACS Applied Materials and In...· 0 citations
Acute kidney injury (AKI) is a clinical syndrome with high incidence and mortality involving oxidative stress, ferroptosis, and inflammation, yet there are no clinically effective interventions. Herein, HA@PDA@EGCG nanoparticles were constructed using polydopamine (PDA) as carriers, loaded with epigallocatechin gallate (EGCG) via π-π stacking, and further surface-modified with hyaluronic acid (HA) through electrostatic interaction. The nanoparticles had uniform morphology with a size of approximately 50 nm and an EGCG loading capacity of 15.4 ± 0.8%. They exhibited prominent broad-spectrum antioxidant activity and hydrogen peroxide-responsive EGCG release, with a cumulative release rate of 58.2 ± 2.2% within 2 h and close to 80% at 12 h. Cellular uptake and in vivo distribution confirmed the efficient CD44 receptor-mediated internalization of the nanoparticles by human kidney-2 (HK-2) cells as well as renal-targeted accumulation. Reactive oxygen species (ROS) staining, mitochondrial morphology and apoptosis assays showed that the nanoparticles effectively scavenged ROS, alleviated mitochondrial damage, and inhibited cell apoptosis. In a cisplatin-induced in vivo AKI model, HA@PDA@EGCG significantly restored renal function: blood urea nitrogen and creatinine decreased to 12.3% and 27.2% of model group levels, respectively, while alleviating renal pathological damage and inflammation. Mechanistically, HA@PDA@EGCG inhibited ferroptosis by downregulating acyl-CoA synthetase long-chain family member 4 (ACSL4) to suppress lipid synthesis, chelating ferrous ions, and stabilizing glutathione peroxidase 4 (GPX4) protein. Collectively, HA@PDA@EGCG achieved renal protection by ameliorating oxidative stress, suppressing inflammation and inhibiting ferroptosis through multiple pathways, offering a novel strategy for targeted AKI therapy.
Elevated intravascular reactive oxygen species (ROS) and persistent inflammation are defining characteristics of the atherosclerotic microenvironment, making their simultaneous modulation a pivotal challenge in cardiovascular therapy. In response, this study presents a groundbreaking plaque microenvironment regulation strategy enabled by self‐propelled nanomotors, referred to as DDMzyme nanomotors, designed specifically for atherosclerosis treatment. These nanomotors autonomously traverse the plaque milieu, catalytically depleting excess hydrogen peroxide and superoxide anions while generating carbon monoxide, a bioactive gas that enhances the targeted accumulation of therapeutic nanoparticles. This synergistic mechanism not only reduces ROS levels during nanomotor movement but also enables additional ROS neutralization through nanozyme payloads delivered directly to the lesion. Functionally, DDMzyme treatment markedly slows atherosclerotic progression by mitigating oxidative stress and promoting cholesterol efflux from macrophages. At the molecular level, DDMzyme activates the NRF2 antioxidant defense pathway by promoting NRF2 dissociation from KEAP1, facilitating its nuclear translocation and the upregulation of downstream cytoprotective genes. This innovation marks a major advancement in precision nanomedicine, introducing a multifunctional, microenvironment‐responsive platform that concurrently targets ROS and inflammation in atherosclerosis.
Hao Tang, Lu Chen, Junyue Xing et al.· Advanced Healthcare Material...· 0 citations
