Advanced Science
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2026
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IF 14.1
Mingquan Gao,Xudong Yu,Ziqian Shang,Mengyao Tan,Xie Huang,Zaizhi Du,Xiaojiao Wang,Xinrui Yang,Ximei Luo,Weidong Wang,Rong Li,Shenglin Luo
Radiation‐induced lung injury (RILI) is a major complication of nuclear radiation exposure and thoracic radiotherapy, driven in part by a vicious cycle of oxidative stress and mitochondrial dysfunction. Peroxisome proliferator‐activated receptor gamma (PPAR‐γ), a key regulator of mitochondrial homeostasis and inflammatory resolution, therefore represents a potential therapeutic target, yet multi‐omics analyses revealed that this immunometabolic checkpoint remains functionally constrained in irradiated macrophages. To reactivate this pathway, we developed an inhalable, ROS‐responsive nanospray (HANP) by loading nicotinamide adenine dinucleotide (NAD + ) and astaxanthin (ASX) into a hollow mesoporous polydopamine (HMPDA) shell. Excess ROS in microenvironment triggers oxidative degradation of the HMPDA shell, enabling intracellular release of NAD + and ASX. Mechanistically, NAD + promotes SIRT1‐mediated deacetylation of PPAR‐γ, whereas ASX serves as an activating ligand, thereby cooperatively restoring PPAR‐γ signaling. This response re‐establishes macrophage mitochondrial homeostasis by coordinating mitochondrial biogenesis and mitophagy, which subsequently promotes a shift toward a reparative macrophage phenotype. In murine models of focal thoracic irradiation and lethal whole‐body irradiation, HANP markedly attenuated lung injury and improved survival. Collectively, these findings identify macrophage PPAR‐γ as a therapeutically actionable redox‐immunometabolic regulator and support inhaled dual‐activation of this pathway as a promising strategy for protection against RILI in both clinical and emergency settings. A nebulized nanoassembly alleviates radiation‐induced lung injury by reprogramming macrophages through coordinated ROS scavenging, NAD + replenishment, and PPAR‐γ activation. Redox balance, mitochondrial homeostasis, and immune regulation are restored, revealing a microenvironment‐centered strategy for localized radioprotection.
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PubMed
高影响因子
Theranostics
·
2026
·Vol. 16
·期 15
·8521
·
IF 14.9
Yipeng Pang,Fructueux Modeste Amona,Hanyuan Liu,Shuming Tang,Jianlong Lao,Xi Chen,Xiaoye Wang
Rationale Chronic diabetic wounds are complicated by multidrug-resistant (MDR) infections and a deleterious oxidative microenvironment, rendering single-target therapies ineffective. This study aimed to develop a smart, dual-metal-organic framework (MOF) nanoplatform (PCNZnCy) capable of microenvironment-responsive, coordinated antibacterial, antioxidant, and pro-regenerative therapy for infected diabetic wounds. Methods The nanoplatform PCNZnCy was constructed by integrating the natural flavonoid chrysin into a zinc-doped porphyrinic MOF (PCN-224), enabling pH- and reactive oxygen species (ROS)-triggered co-release of Zn²⁺ and chrysin. Antibacterial and anti-biofilm activity was assessed against biofilm-embedded MDR pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA). Antioxidant and signaling effects were evaluated by measuring ROS scavenging, mitochondrial function, endothelial cell proliferation, and activation of Nrf2/HO-1, STAT3, and Akt pathways, with confirmation using the Nrf2 inhibitor ML385. To assess efficacy and safety in a clinically meaningful setting, we used a diabetic murine wound model infected with P. aeruginosa and a systems-level transcriptomic analysis to capture the broader tissue response. Results We found that PCNZnCy showed strong synergistic antibacterial activity against MRSA and PA. Beyond that, it scavenged excess ROS, triggered Nrf2/HO-1 signaling, modulated STAT3 and Akt signaling, preserved mitochondrial health, and spurred endothelial cell growth. In diabetic mice, wounds healed faster, with improved collagen deposition and increased formation of new blood vessels, while the compound remained safe. RNA-seq data underscored a decisive move from pro-inflammatory to pro-regenerative gene expression. Conclusions PCNZnCy adapts to the wound's specific microenvironment, enabling it to kill bacteria, reduce oxidative stress, and promote tissue regeneration. In the infected diabetic models, it worked consistently well. This makes it a strong candidate for multifactorial, complex wound pathologies, in which multiple complications overlap.
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Materials Today Bio
·
2026
·
IF 11
Zhaohua Yang,Shutian Zhang,Wenrui Ma,Hongqiang Zhang,Shouguo Yang,Xiaoning Sun,Mengni Zhu,Chunsheng Wang,Yixuan Wang
Heart transplantation offers the only life-saving option for patients with terminal heart failure; yet, the sequential "innate-adaptive" avalanche initiated by ischemia-reperfusion injury (IRI) remains the Achilles' heel of long-term graft acceptance. Current regimens overwhelmingly focus on either the adaptive or the IRI-triggered innate arm, failing to interrupt the positive-feedback loop that amplifies allo-rejection. To address this unmet need, we herein present a single ROS-responsive nanoplatform that weds dual immunosuppression with on-demand oxygenation Fe 3 O 4 @CaO 2 @Tac@HA. The core-shell Fe 3 O 4 @CaO 2 carrier simultaneously loads hyaluronic acid (HA), which is a potent dampener of innate inflammatory signaling, and tacrolimus (Tac), which is a calcineurin inhibitor that arrests adaptive T-cell activation. Upon exposure to the ROS-rich milieu of the reperfused graft, CaO 2 undergoes conversion to O 2 , promptly relieving tissue hypoxia while reducing oxidative stress. In vitro , the nanocomposite exhibits rapid ROS scavenging, sustained oxygen release and inhibit T cell activation; in vivo, it markedly prolongs cardiac-allograft survival by synchronously suppressing innate immune cells infiltration and CD8 + T-cell cytotoxicity. Collectively, Fe 3 O 4 @CaO 2 @Tac@HA offers a translatable "one-two punch" strategy that unites innate and adaptive immunomodulation, setting the stage for precision nanotherapy in cardiac transplantation.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2026
·
IF 9.6
Ran Gao,Xinqi Xu,Yingzi Zhou,Chenyang Lan,Zhuobin Xu,Dandan Li,Hao Chen,Ke Li,Huihui Wang
The migratory capacity and invasiveness of tumor cells are critically dependent on two key cellular features: lamellipodia formation at the leading edge of cells and the structural integrity of lipid rafts. Within the tumor microenvironment (TME), cholesterol (Ch), a core lipid raft constituent, is frequently observed to be overabundant. Excess Ch promotes cancer cell proliferation, enhances tumor cell motility, induces epithelial-mesenchymal transition (EMT), and elicits immunosuppressive effects. However, there remains a lack of targeted and effective strategies to normalize excess Ch levels in tumor lesions. Herein, we fabricated a cascade catalytic nanozyme (CHO@Cu/His-ZIF8) via in-situ mineralization of cholesterol oxidase (CHO) within L-histidine (His)-modified Cu-ZIF8. This nanozyme not only mimics the catalytic activity of natural peroxidase (POD) to achieve self-amplified reactive oxygen species (ROS) generation (CHO oxidizes Ch to produce H₂O₂; the catalase-like activity of the nanozyme simultaneously decomposes partial H₂O₂ to generate O₂, which further accelerates Ch consumption by CHO; meanwhile, the POD-like activity converts H₂O₂ into highly toxic •OH), but also degrades excess Ch to disrupt lipid rafts and lamellipodia, thereby inhibiting tumor cell migration and invasion. In vivo studies confirmed that CHO@Cu/His-ZIF8 effectively accumulated at tumor sites and exhibited excellent biocompatibility. Experiments in subcutaneous tumor models, lung metastasis models, and bilateral tumor models consistently demonstrated that CHO@Cu/His-ZIF8 exerts potent and highly efficient antitumor efficacy, especially in inhibiting tumor metastasis, highlighting its promising clinical translation potential. Schematic representation of CHO@Cu/His-ZIF8 for combined treatment involving cholesterol depletion and ROS upregulation. Download: Download high-res image (181KB) Download: Download full-size image
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高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Ming Zhu,Shimin Dai,Jingquan Cui,Zhibo Zhao,Xingchen Wei,Ping Li,Wei Li
ROS-responsive hydrogel delivers CircSERPINE2-engineered exosomes. • Boronate ester cleavage scavenges ROS for controlled exosome release. • BV@cSERPINE2-Exo promotes M2 macrophage polarization and chondrogenesis. • Intra-articular injection yields near-complete hyaline cartilage repair. Osteoarthritis (OA) involves chronic inflammation and oxidative stress, both of which impair cartilage regeneration. To counteract these pathological processes, bone marrow mesenchymal stromal cell (BMSC)-derived exosomes have emerged as a promising therapy. These exosomes promote chondrogenesis and facilitate chemokine-guided cell homing. However, hostile microenvironments compromise their efficacy. This study developed a cell-free, ROS-responsive boronate-vinyl (BV) hydrogel platform encapsulating BMSC-derived exosomes overexpressing CircSERPINE2 (BV@cSERPINE2-Exo), which were isolated via ultracentrifugation from lentivirus-transduced BMSCs. This platform enables sustained microenvironmental modulation and functional cartilage regeneration. The hydrogel forms through dynamic boronate ester crosslinking between phenylboronic acid-modified poly γ-glutamic acid and polyvinyl alcohol (PVA). It exhibits rapid gelation, shear-thinning injectability, and potent ROS-scavenging capacity. ROS-triggered cleavage of the boronate ester bonds ensures controlled exosome release. In vitro, BV@cSERPINE2-Exo shifted LPS-stimulated macrophages from an M1 to M2 phenotype by decreasing iNOS and IL-1β levels and increasing Arg-1 and IL-10. Concurrently, the system protected chondrocytes from TNF-α-induced degeneration by downregulating MMP13 and restoring COL2A1, SOX9, and proteoglycan synthesis. In a rat patellar cartilage defect model, intra-articular injection of BV@cSERPINE2-Exo promoted deposition of cartilage-specific extracellular matrix and achieved near-complete hyaline cartilage-like repair within 8 weeks. This repair was superior to that in the BV hydrogel or unmodified exosome control groups. These results establish a smart, injectable biomaterial strategy that integrates precise ROS-responsive circRNA delivery with immunomodulation, offering a promising early intervention strategy for cartilage defect repair and the prevention of osteoarthritis progression.
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高影响因子
Materials Today Bio
·
2026
·
IF 11
Yu He,Xiaoqi Yang,Yongke Bai,Xiaozhuo Ba,Tao Ye,Zichen Zhong,Zhiqiang Chen,Heng Li,Kun Tang
Calcium oxalate (CaOx) nephrocalcinosis is a chronic kidney disease marked by CaOx crystal deposition, oxidative stress, neutrophil infiltration, and renal tubular epithelial cell injury. To date, no targeted therapies are clinically available for this condition. Antioxidant nanomaterials capable of scavenging excessive reactive oxygen species (ROS) offer a promising approach for treating CaOx crystal-induced kidney injury. Neutrophil-mediated delivery systems have been leveraged to transport nanomaterials to inflamed kidneys for acute kidney injury therapy, and their targeting specificity can be further augmented through the functionalization of cell membranes with targeting peptides. Herein, we developed a biomimetic nanoplatform by loading DNase I onto black phosphorus nanosheets (BPNSs) and coating them with a neutrophil membrane modified with a CD44-targeting peptide (PNM@D@BP), aiming to ameliorate renal CaOx crystal deposition and the consequent kidney injury. The engineered neutrophil membrane coating conferred the nanocarrier with the ability to home to sites of renal injury and inflammation. PNM@D@BP exhibited potent antioxidative activity, effectively eliminating CaOx crystal-induced ROS. In both in vivo and in vitro settings, PNM@D@BP was shown to suppress the formation of neutrophil extracellular traps (NETs). Moreover, RNA sequencing and bioinformatic analyses revealed that PNM@D@BP protects against CaOx crystal-induced kidney injury by modulating oxidative stress and neutrophil-driven inflammatory responses. Collectively, these findings underscore the therapeutic potential of PNM@D@BP for the treatment of CaOx kidney stones.
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高影响因子
Materials Today Bio
·
2026
·
IF 11
Xiaoqing Zhou,Guangyun Hu,Can Huang,Ying Liu,Zhou-rui Ma,Yuangang Lu,Yong Xu,Wei Qian
Intractable wounds remain a major clinical challenge due to persistent oxidative stress, dysregulated inflammation, and impaired macrophage polarization. Here, we develop a therapeutic cryogel by integrating ultrasmall Prussian blue (USPB) nanozymes into a GelMA–quaternary ammonium chitosan methacryloyl matrix via cryogelation. The resulting Cryogel@USPB features high porosity, large interconnected pores, and strong swelling capacity, supporting its application in wound environments. Cryogel@USPB exhibits potent catalase-, peroxidase-, and superoxide dismutase-like activities, enabling efficient ROS scavenging. In vitro, it promotes macrophage polarization toward a regenerative phenotype and suppresses pro-inflammatory cytokines. In vivo, Cryogel@USPB significantly accelerates healing in deep second-degree burn and diabetic wound models, achieving wound closure rates of 94.07 ± 1.94% and 98.69 ± 1.02%, respectively, with improved skin structure and collagen deposition. Mechanistically, Cryogel@USPB modulates the wound microenvironment by inhibiting cGAS–STING signaling. These findings identify Cryogel@USPB as a promising immuno-regulatory nanozyme platform for treating complex wounds.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2026
·
IF 12.4
Keqiang Lu,Yaoquan Su,Xingchen Zhou,Fang Zhang,Xueping Zeng,Zikun Wang,Jiayu Gu,Yunyun Zhou,Jinfeng Liu,Juanjuan Peng,Lingzhi Zhao
Conventional reactive oxygen species (ROS)-mediated tumor therapies such as photo-, sono-, and chemodynamic therapies are often limited by inadequate penetration depth of external stimuli and insufficient endogenous ROS substrates (e.g., O₂ and H₂O₂). Here, we report that horseradish peroxidase (HRP) can catalyze artemisinin to generate ROS. Based on this, a “ROS bomb” nanomedicine was designed for antitumor immunotherapy. The nanocarrier consists of silica cross-linked micelles incorporating ROS-cleavable thioketal bonds and encapsulated artemisinin as the payload, with surface-immobilized HRP serving as the trigger. Within the tumor microenvironment with elevated H₂O₂, the thioketal linkers are cleaved to release artemisinin, initiating an HRP-catalyzed ROS cascade. The ROS burst induces immunogenic cell death and activates the STING pathway in dendritic cells assisted by the co-released drug SN38, effectively suppressing the growth of immunosuppressive triple-negative breast tumors. This exogenous ROS delivery strategy overcomes the restrictions of conventional ROS therapies, offering a potent approach for treating deep-seated tumors.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·208
·
IF 15
Su Chenyu,Xu Kangwen,Xing Xuexia,Liu Yuan,Yang Yahui,Zhao Donglin,Zhang Chengsheng
Background 2 E ,4 E -decadienoic acid (DDA) is an aliphatic compound with potent anti‑oomycete activity against Phytophthora nicotianae (Pn), a plant pathogen responsible for major agricultural losses. Mechanistic studies revealed that DDA targets mitochondria and requires intracellular delivery to exert its activity. To improve its stability and bioavailability, we developed a reactive oxygen species (ROS)–responsive, TAT‑peptide (P) ‑modified liposomal (Lipo) delivery system (DDA@P‑ROS‑Lipo) containing thioketal (TK) linkages that cleave under elevated ROS conditions during pathogen infection, enabling controlled and site‑specific release of DDA. The TAT peptide, as a cell‑penetrating moiety, markedly enhanced intracellular uptake. Results The resulting nanoparticles exhibited an average hydrodynamic diameter of approximately 112 nm and a high DDA encapsulation efficiency of 80.84%. They also demonstrated excellent photostability, making the formulation suitable for field application. The nanoscale size and strong affinity for tobacco leaf surfaces reduced the contact angle, thereby improving adherence and deposition. Compared with free DDA, the nanoformulation enhanced mycelial inhibition by 45% and achieved superior control of tobacco black shank disease in pot experiments. Both in vitro cytotoxicity and in vivo zebrafish toxicity assays confirmed the safety of the formulation. Conclusion This work presents a simple and effective strategy for the targeted delivery of anti‑oomycete agents. DDA@P‑ROS‑Lipo offers a green and efficient approach for plant disease management under controlled conditions, and future studies will explore its scalability and performance in field environments. Graphical
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高影响因子
Advanced Healthcare Materials
·
2026
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IF 11
Jiepei Lin,Min You,Xinbei Lv,Vanessa Vimbiso Mavhunure,Qinying Wang,Ziqing Tang,Hui Yu,Qiang Chen,Feng Lin,Huijuan Hu
Intrauterine adhesion (IUA) leads to abortion and infertility that poses a severe threat to female reproductive and psychological health. The highly oxidative microenvironment and fibrosis of the endometrial wound are critical factors driving IUA pathogenesis. Here, a pH and reactive oxygen species (ROS) dual-responsive hydrogel (DRH) with antifouling property, which could be gelated in situ click chemistry, was developed to effectively treat IUA via anti-oxidative and anti-fibrosis. This DRH was prepared by a dual-crosslinking structure, which was based on the thiol-ene click chemistry reaction of poly(ethylene glycol) diacrylate (PEGDA), 4-arm poly(ethylene glycol) acrylate (4-arm-PEG-AC) and dithiothreitol (DTT), coupled with borate ester bonds between borax and DTT. This DRH presented excellent antifouling and good ROS scavenging, which reduced protein and cell adhesion, as well as alleviated oxidative stress. Additionally, the DRH also exhibited pH and ROS responsiveness, enabling degradation in the intrauterine microenvironment. In the rat endometrial injury model, the DRH successfully exerted an effective therapeutic effect on IUA, and thus eventually restored fertility by attenuating the endometrial oxidative damage, inhibiting the activation of myofibroblasts, and reducing epithelial-mesenchymal transition.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Deng Xu,Xie Xixiang,Zhou Xing,Jiang Lanfang,Zhu Tao,Su Rixiang,Chen Chunmei,Chen Wan,Chen Chunxia
The therapeutic efficacy of ischemic stroke (IS) treatment is severely limited by insufficient accumulation of therapeutic agents within ischemic lesions and persistent secondary injury after ischemia–reperfusion. Herein, we report a cRGD-functionalized exosome-based nanoplatform that enhances ischemic lesion-associated accumulation and antioxidative neuroprotection for the treatment of IS. Neural stem cell-derived exosomes were functionalized with cyclic RGD peptides (cRGD) and subsequently loaded with Mn₃O₄ nanoparticles to construct a hybrid nanosystem (cRGD-Exo@Mn₃O₄). The engineered exosomes preserve intrinsic brain tropism, while cRGD modification promotes preferential accumulation in ischemic regions, potentially through interaction with α v β 3 integrin that is upregulated in ischemic lesions. The incorporated Mn₃O₄ nanoparticles confer robust reactive oxygen species (ROS) scavenging capability, thereby mitigating oxidative stress in ischemic microenvironments. In vitro and in vivo studies demonstrate that cRGD-Exo@Mn₃O₄ exhibits enhanced accumulation in ischemic regions compared with non-modified counterparts. The nanosystem effectively attenuates oxidative stress and neuroinflammation, leading to reduced infarct volume, alleviation of cerebral edema, and improved neurological function in MCAO/R mice. Mechanistically, transcriptomic analysis suggests that the therapeutic effects are associated with modulation of inflammation-and cell death-related pathways, including suppression of the RIPK1/RIPK3/MLKL signaling cascade. Collectively, this study presents a rationally designed exosome-based nanoplatform integrating ischemic lesion-associated accumulation with ROS-scavenging capability. Graphical abstract
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Tiantian Cui,Bing Li,Zhaoyang Lou,Kai Yang,Kaijin Yan,Danhong Ding,Hong Ge
Inflammatory bowel disease (IBD) represents a group of chronic, non-specific gastrointestinal disorders characterized by pathological overproduction of reactive oxygen species (ROS). Current therapeutic interventions, including conventional drugs and oral probiotics, are frequently limited by their vulnerability to the harsh gastrointestinal environment. To address these challenges, we have developed a novel engineered bacterium, designated as CeO₂@EcN-L, through the integration of cerium oxide nanozymes (CeO₂) with the probiotic strain Escherichia coli Nissle 1917 (EcN), followed by encapsulation with a pH-responsive anionic copolymer composed of methacrylic acid and ethyl acrylate (Eudragit L100–55). The negatively charged surface of the Eudragit L100–55 coating enables CeO₂@EcN-L to not only selectively adhere to positively charged inflamed colon tissues through electrostatic interactions but also achieve sustained release of therapeutic agents throughout the gastrointestinal tract. Upon accumulation in the inflamed colon, the CeO₂ component demonstrates dual enzymatic activities, mimicking both catalase (CAT) and superoxide dismutase (SOD), which collectively facilitate efficient ROS scavenging and subsequent inflammation alleviation. In a dextran sulfate sodium (DSS)-induced murine IBD model, CeO₂@EcN-L demonstrate remarkable anti-inflammatory efficacy and significantly restore gut microbiota homeostasis. This study establishes a novel, safe, and effective therapeutic strategy for IBD treatment, offering promising potential for clinical translation.
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