Advanced Science
·
2026
·
IF 14.1
Mofan Li,Mengxin Wang,Haonan Wang,Yang Sun,Yongyue Zhang,Shuyu Xu,Tianjiao Zhang,Shiti Shama,Xiaolong Liang,Shumin Wang
Diabetic wound (DW) is a diabetes complication characterized by high morbidity and disability rates. Previous therapeutic systems focused on macrophages while neglecting the upstream regulatory factor of neuropeptide-mediated neuroimmune communication. In addition, precise delivery is directly important for the treatment of DW. This study constructed an amphiphilic prodrug molecule MC by covalently conjugating calcitonin gene-related peptide (CGRP) with manganese porphyrin (MnP). MC was then co-assembled with DSPE-PEG-folic acid to form targeted nanoparticles MCF. Subsequently, MCF was loaded into an ultrasound-responsive hydrogel to obtain the MCF@CA system, integrating neuroimmune modulation and reactive oxygen species (ROS) scavenging functions. Upon local administration, ultrasound triggering enables the on-demand release of the nanodrug MCF from MCF@CA. Subsequently, FA targets M1 macrophages, prolonging wound retention time. MnP scavenges ROS, improving fibroblast function and promoting macrophage polarization towards an anti-inflammatory phenotype. This study presents an ultrasound-responsive hydrogel MCF@CA delivering targeted nanoparticles where CGRP regulates the regenerative transition of the immune microenvironment. Animal experiments confirmed that MCF@CA combined with ultrasound significantly promotes DW healing by enhancing collagen deposition, immune modulation, and improving blood supply. Therefore, this study provides an on-demand controlled delivery platform with clear translational potential for diabetic wound therapy.
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PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 10.2
Yongkang Lai,Yongliang Ouyang,Xiaojing Yin,Tao Yu,Jianhua Wan,Xueyang Li,Yi Hu,Xu Shu,Huan Wang
Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal–organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered in vivo , the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce 3+ and Ce 4+ , while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.
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高影响因子
Journal of Future Foods
·
2026
·
IF 7.2
Linlin Hao,Yinxue Liu,Yisuo Liu,Lu Jiang,Ignatius Man-Yau Szeto,Tongjie Liu,Huaxi Yi
Probiotics represents a significant strategy for managing inflammatory bowel disease (IBD), however, the inflammatory gut microenvironment rich in reactive oxygen species (ROS) compromises the viability and colonization of probiotics. Here, we innovatively developed a ROS-responsive probiotic delivery system based on milk exosomes (mExo@DSPE-PEG-PBA@AKK). The ROS-sensitive borate ester bond in mExo@DSPE-PEG-PBA@AKK underwent oxidation and cleavage at inflammatory sites, which simultaneously scavenged excessive ROS and achieved targeted release of the probiotics. Consequently, mExo@DSPE-PEG-PBA@AKK exhibited enhanced activity and prolonged retention within the inflamed intestine. In dextran sulfate sodium (DSS)-induced colitis mice, mExo@DSPE-PEG-PBA@AKK showed superior therapeutic efficacy compared to treatment with milk exosomes or probiotics alone. Furthermore, mExo@DSPE-PEG-PBA@AKK treatment reduced pro-inflammatory factor levels, restored intestinal barrier integrity, and effectively modulated the abundance and diversity of the gut microbiota in DSS-induced mice. The proposed mExo@DSPE-PEG-PBA@AKK system incorporates multiple functions including probiotic protection, delivery, and targeted release, offering a novel “clear-release-regulate” therapeutic approach for the treatment of IBD.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xianshuo Zhang,Peipei Wang,Xinsheng Wang,Yaoyu Xu,Taolin Cheng,Chengjie Zhang,Jiaying Ding,Yunfeng Shi,Wei Ma,Cui-Yun Yu,Hua Wei
Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility , biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β -cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly( ε -caprolactone)- b -poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL- b -PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL- b -PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% ( P1 ) and 20 wt% ( P2 ) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1 -based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1 -based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.
研究领域:
纳米医学
·
癌症研究
·
药物递送系统
·
材料科学
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高影响因子
DIABETES
·
2025
·Vol. 74
·期 12
·2405-2417
·
IF 7.5
Guo Lei,Wu Peili,Li Qing,Feng Qijian,Lin Xiaochun,Luo Yuling,Wang Yuan,Wu Minghai,Cai Feifei,Zhang Jin,Hu Yuxuan,Wang Huiyun,Wang Yu,Luo Sirui,Tian Linlin,Fan Xinzhao,Wang Ling,Xue Yaoming,Guan Meiping
Diabetic kidney disease (DKD) progression involves intricate interactions among senescence, oxidative stress, inflammation, and fibrosis. This study systematically investigates the regulatory role and molecular mechanisms of NUAK1 in DKD pathogenesis. Bioinformatics analysis of Gene Expression Omnibus data sets identified NUAK1 as a differentially expressed gene, validated in human kidney proximal tubule epithelial (HK-2) cells, high-fat diet and streptozotocin-induced DKD mice, d -galactose–induced senescent mice, and human peripheral blood mononuclear cells. Functional studies demonstrated that NUAK1 inhibition via siRNA knockdown, pharmacological inhibitors, or kidney tubule-targeted adeno-associated virus serotype carrying shRNA against NUAK1 delivery attenuated reactive oxygen species–tumor protein 53 (ROS/P53) axis-mediated renal tubular senescence, oxidative stress, inflammation, and fibrosis in vitro and in vivo. Mechanistically, chromatin immunoprecipitation quantitative PCR revealed that transcription factor ETS1 directly binds to the NUAK1 promoter, driving its transcriptional activation in DKD. Furthermore, molecular docking and dynamics simulations identified Asiatic acid (AA) as a potent NUAK1 inhibitor, with a stable binding affinity. AA suppressed NUAK1 expression and downstream pathological processes, ameliorating renal injury in DKD models. These findings elucidate the role and regulatory mechanisms of NUAK1 in modulating ROS/P53 axis-driven tubular senescence and oxidative stress, providing a theoretical basis for structure optimization in drug development targeting NUAK1. Article Highlights Mechanisms linking renal tubular senescence to diabetic kidney disease (DKD) progression remain poorly understood. Systematic elucidation of the regulatory role of NUAK1 in the pathogenesis of DKD and its regulatory mechanisms is provided. NUAK1 is upregulated in DKD, promoting senescence via reactive oxygen species–tumor protein 53 under transcriptional activation by E26 transformation–specific 1, while Asiatic acid (AA) directly binds NUAK1 to suppress these pathological processes. NUAK1 emerges as a therapeutic target for DKD, and AA provides a natural scaffold for NUAK1 inhibitor development, offering a strategy to combat diabetes-related renal decline.
研究领域:
肾脏病学
·
分子生物学
·
糖尿病研究
·
药理学
·
衰老研究
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PubMed
高影响因子
Exploration
·
2024
·
IF 0
JunJie Tang,Yadong Liu,Yifan Xue,Zhaozhong Jiang,Baizhu Chen,Jie Liu
Prodrug-based self-assembled nanoparticles (PSNs) with tailored responses to tumor microenvironments show a significant promise for chemodynamic therapy (CDT) by generating highly toxic reactive oxygen species (ROS). However, the insufficient level of intracellular ROS and the limited drug accumulation remain major challenges for further clinical transformation. In this study, the PSNs for the delivery of artesunate (ARS) are demonstrated by designing the pH-responsive ARS-4-hydroxybenzoyl hydrazide (HBZ)-5-amino levulinic acid (ALA) nanoparticles (AHA NPs) with self-supplied ROS for excellent chemotherapy and CDT. The PSNs greatly improved the loading capacity of artesunate and the ROS generation from endoperoxide bridge using the electron withdrawing group attached directly to C10 site of artesunate. The ALA and ARS-HBZ could be released from AHA NPs under the cleavage of hydrazone bonds triggered by the acidic surroundings. Besides, the ALA increased the intracellular level of heme in mitochondria, further promoting the ROS generation and lipid peroxidation with ARS-HBZ for excellent anti-tumor effects. Our study improved the chemotherapy of ARS through the chemical modification, pointing out the potential applications in the clinical fields.
研究领域:
药理学
·
生物医学工程
·
肿瘤学
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DOI
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.5
Lei Nie,Xiaoyue Ding,Yiran Lin,Letian Yan,Yanting Han,Yuanna Sun,Yanfang Sun,Guohua Jiang
Decellularized extracellular matrix (dECM) has been widely used in tissue engineering and regenerative medicine due to its excellent biocompatibility and biological activities. In this work, the dECM was obtained by treating porcine Achilles tendon tissue via a combination of chemical, physical, and biological approaches. The obtained dECM was interpenetrated with genipin crosslinked quaternary ammonium chitosan (QCS) network to fabricate the composite genipin/QCS/dECM (QGD) hydrogels. The prepared QGD hydrogels exhibited an interconnected microstructure and a suitable water-absorption capacity. Furthermore, the QGD hydrogels exhibited strong adhesion to the surfaces of different matrices and various organs, including lung, liver, trachea, heart, and spleen. The remodelling of dECM gave the QGD hydrogels adjustable self-healing ability and mechanical properties. In addition, the QGD bio-adhesives exhibit effective antibacterial activity against the typical Gram-positive S. aureus and Gram-negative E. coli . 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging tests confirmed the antioxidant abilities of QGD hydrogels, and the cellular reactive oxygen species (ROS) scavenging potential was also investigated using RAW264.7 cells. Furthermore, the QGD hydrogels possessed excellent hemocompatibility, cytocompatibility, and cell pro-migration abilities. The results confirmed that the proposed QGD hydrogels could serve as potential bioadhesives for biomedical applications.
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Translational Cancer Research
·
2026
·Vol. 15
·期 7
·555
·
IF 2.1
Junjie Wu,Congxing Liu,Yaya Sun,Guangqing Jiang,Yupeng Zhao,Yihong Zhang,Yiping Yin,Xin Shi
Background Colon cancer (CC) is a heterogeneous disease with increasing morbidity and mortality. Ferroptosis, a recently identified form of regulated cell death (RCD) characterized by the massive accumulation of iron-dependent lipid peroxidation (LPO), has been proven to be closely associated with various biological behaviors of CC. Moreover, accumulating evidence reveals that ALOX12 is essential for p53-mediated ferroptosis through distinct pathways. Therefore, our study aims to explore the specific mechanisms by which ALOX12 regulates tumorigenesis in CC through ferroptosis pathway. Methods We explored the characteristics of ALOX12 expression and its correlation with prognosis in CC patients and cell lines, followed by a series of functional assays in vitro and in vivo to investigate the mechanisms underlying the functions of ALOX12 in p53-driven ferroptosis. Results We discovered that ALOX12 was downregulated in CC tissues and cell lines, which was correlated with poor prognosis. Furthermore, overexpression of ALOX12 suppressed cell proliferation and tumorigenesis by upregulating reactive oxygen species (ROS)-induced stress. We continuously found that increased ALOX12 levels enhanced the sensitivity of CC cells to a distinct ferroptosis, which required both p53 activation and additional ROS, and differed from that induced by erastin. Conclusions Our study demonstrates the oncosuppressive behavior of ALOX12 in CC. Mechanistically, we discover that p53 can indirectly activate ALOX12 function by suppressing its transcriptional target SLC7A11, resulting in an ALOX12-dependent ferroptotic pathway. Targeting ALOX12 may provide a novel biomarker or new therapeutic strategies for improving the prognosis of CC.
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高影响因子
ACS ES&T Water
·
2026
·
IF 4.5
Zhan Qihong,Rao Zepeng,Xiao Xin,Chen Baoliang
Micronanobubbles
(MNBs) offer enhanced interfacial area and distinct
interfacial physicochemical properties, but the mechanistic role of
interfacial charge in governing ozone-derived reactive oxygen species
(ROS) remains inadequately understood. Herein, the pH-dependent interfacial
charge characteristics of ozone micronanobubbles (O 3 -MNBs)
were systematically examined to elucidate their influence on sulfamethoxazole
(SMX) degradation. O 3 -MNBs increased the apparent degradation
rate by approximately 4-fold relative to macrobubbles, with initial
enhancement driven by facilitated ozone dissolution and subsequent
acceleration governed by interfacial reaction processes. ζ potential
measurements and ROS probe analyses demonstrated that solution pH
modulates MNB interfacial charge, thereby regulating pollutant interfacial
enrichment and shifting ROS dominance. Acidic conditions promoted
hydroxyl radical ( • OH) formation through interfacial
instability, whereas neutral and alkaline conditions favored the generation
of superoxide radicals (O 2 •– )
and singlet oxygen ( 1 O 2 ). Quadrupole time-of-flight
mass spectrometry (Q-TOF-MS) further confirmed that these distinct
ROS regimes correspond to divergent SMX transformation pathways. The
findings establish interfacial charge regulation as a critical determinant
of reaction selectivity in O 3 -MNB systems and provide mechanistic
guidance for optimizing MNB-assisted ozonation in advanced water treatment.
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ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Li Xiang,Mao Yuemiao,Ye Bo,Li Ming,Hou Jianwen,Liu Xia
Chronic diabetic wounds represent a severe complication of diabetes mellitus and a prototypical form of chronic nonhealing wounds, characterized by biofilm-associated infection, persistent inflammation, and impaired angiogenesis. Herein, a multifunctional microneedle platform incorporating cationic chitosan-coated ruthenium dioxide nanozymes (RuO 2 @QCS NPs), termed RuO 2 @QCS-MN, is developed to accelerate diabetic wound healing through microenvironment reprogramming. This integrated system combines photothermal antibacterial activity, reactive oxygen species (ROS) scavenging, and in situ oxygen generation to coordinately regulate the pathological milieu of infected wounds. The microneedles effectively penetrate bacterial biofilms and deliver nanozymes to bacteria-enriched regions, enabling efficient yet mild photothermal antibacterial therapy. Meanwhile, RuO 2 @QCS NPs exhibit catalase-like activity, catalyzing endogenous hydrogen peroxide into oxygen, thereby enhancing nanozyme diffusion, alleviating oxidative stress, modulating inflammatory responses, and promoting macrophage polarization. Simultaneous oxygen generation may alleviate hypoxia and promote angiogenic responses. Both in vitro and diabetic in vivo models demonstrate efficient bacterial elimination, inflammation suppression, and enhanced re-epithelialization and neovascularization, ultimately accelerating wound repair. This work establishes a highly integrated nanozyme-enabled therapeutic paradigm for the localized treatment of infected diabetic wounds.
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高影响因子
BIOMACROMOLECULES
·
2026
·Vol. 27
·期 8
·5795-5806
·
IF 5.9
Yang Xue,Huang Menglin,Wu Hongjing,Li Wen,Chen Hongqi,Dai Xiaomei,Gao Feng
Bacterial pneumonia, a prevalent respiratory disease
with high
global morbidity and mortality rates, remains a formidable therapeutic
challenge. Herein, pH/reactive oxygen species (ROS) dual-responsive
zwitterionic polymer (PODEA- b -P(ROS-CA-EG)n) micelles
are developed for bacterial pneumonia therapy. The zwitterionic shell
can facilitate the micelles to effectively penetrate through the mucus.
These micelles exhibit pH-responsive charge reversal performance,
which is conducive to the cellular internalization and bacterial killing.
Meanwhile, the micelles respond to the acid and overexpressed ROS
microenvironment at the lesion site to release cinnamaldehyde (CA),
enhance ROS generation, and activate an immune reaction to eliminate
extracellular and intracellular bacteria collaboratively. In bacterial
pneumonia, PODEA- b -P(ROS-CA-EG)n micelles can effectively
eliminate bacteria and alleviate lung inflammation. These pH/ROS dual-responsive
zwitterionic polymer micelles could provide a synergistic therapeutic
strategy against bacterial pneumonia.
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EUROPEAN JOURNAL OF PLANT PATHOLOGY
·
2026
·
IF 2.1
Qu Huan,Yang Ershuai,Li Zongze,Li Yaoxuan
Dimethyl trisulfide (DMTS) exhibits potent antifungal activity against Alternaria alternata , yet its molecular mode of action has not been fully elucidated. In this study, we analyzed the key gene expression and phenotypic alterations in A. alternata after DMTS treatment to clarify its potential antifungal mechanism, and to provide insight into possible fungicidal targets. Given the pronounced antifungal activity of DMTS, transcriptomic analysis was performed to profile global gene expression changes in A. alternate following DMTS exposure, complemented by bioinformatics analysis and real-time fluorescent quantitative PCR (RT-qPCR) validation. A total of 2,321 differentially expressed genes (DEGs) were identified, including 934 up-regulated and 1,387 down-regulated genes. RT-qPCR validation confirmed that the gene expression trends were consistent with the transcriptomic data, supporting the reliability of the sequencing results. GO functional annotation and KEGG enrichment analysis revealed that the DEGs were associated with peroxisome formation, fatty acid β -oxidation, cellular ROS homeostasis, and energy metabolism pathways such as the tricarboxylic acid (TCA) cycle. In line with these transcriptional changes, DMTS exposure caused substantial intracellular ROS accumulation, impaired mitochondrial activity, reduced ATP production and DNA fragmentation, reflecting significant bioenergetic impairment and redox imbalance. Collectively, these findings suggest that DMTS inhibits fungal growth by disrupting peroxisome formation, mitochondrial function, and triggering excessive ROS-mediated oxidative damage. Simultaneously, DMTS impedes fatty acid β -oxidation and the TCA cycle, resulting in significant cellular ATP depletion. These combined effects ultimately inhibited the growth of A. alternata .
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