CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Jianqiu Yang,Zhenyu Chen,Tao Zhang,Rongxiang Hu,Dingguo Wang,Shiwei Chen,Lingxian Zhang,YunFeng Ge,Yongbing Wu
Hybrid macrophage/cardiomyocyte membrane coating achieves immune evasion and myocardial targeting. • Pomelo peel cellulose-based microneedles enable 14-day sustained release of ginsenoside Rg1. • The system blocks the mtDNA-cGAS-STING inflammatory axis by preserving mitochondrial integrity. • Treatment promotes M2 macrophage polarization and angiogenesis in infarcted myocardium. • CM@PPG-MNs significantly improve survival and cardiac function in rat myocardial infarction. Myocardial infarction (MI) leads to severe inflammatory reaction and mitochondrial damage, which will inevitably lead to heart failure. There are many problems in the application of traditional nano-carriers, especially the facts that they are easily cleared quickly by the immune system, have poor heart targeting and release drugs too fast. In order to overcome the above problems, a hybrid cell membrane targeted delivery system was designed in this study. In this system, macrophage membrane and myocardial cell membrane were fused, and ginsenoside Rg1 was encapsulated, and then the complex was loaded into a natural pomelo peel cellulose hydrogel microneedle patch to form CM@PPG-MNs. The macrophage membrane component in the carrier can help it escape from immune system attack, while the myocardial cell membrane component can accurately target the damaged myocardial tissue. The microneedle patch can penetrate the surface of the heart and realise the controlled release of ginsenoside Rg1 within the critical 14-day treatment cycle. Studies have confirmed that the system can stop the vicious cycle of inflammation and mitochondrial damage by blocking the mtDNA-cGAS-STING pathway, and at the same time promote the polarization of macrophages from pro-inflammatory M1 type to repair-oriented M2 phenotype. In the rat model of myocardial infarction, the treatment of CM@PPG-MNs patch significantly improved the survival rate of the model animals and reduced the mortality rate from 54.17% to 16.67%. The natural microneedle system developed in this study has excellent efficacy and high application potential in the field of myocardial repair. Schematic illustration of the synthesis, in vivo delivery, and intracellular mechanisms of the macrophage membrane-camouflaged biomimetic microneedle patch (CMV-RG1 Bio-MN Patch) for myocardial infarction treatment, detailing the extraction of cellulose nanofibers and RAW 264.7 macrophage membranes to fabricate a microneedle patch loaded with Rg1 encapsulated nanovesicles (Rg1@CM), which, upon implantation onto the infarcted area, utilizes homologous “self” recognition to evade host macrophage attack and specifically target injured cardiomyocytes, where Rg1 exhibits a dual-pathway blockade by inhibiting the mtDNA-triggered cGAS-STING inflammatory pathway (downregulating IL-1β, IL-6, TNF-a and upregulating IL-4, IL-10) and preventing mitochondrial Cytochrome c release to mitigate ATP depletion, synergistically promoting ROS scavenging, angiogenesis, and M2 macrophage polarization. Download: Download high-res image (200KB) Download: Download full-size image
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Nan Wang,Shiyu Ma,Fangyu Jiao,Zhe Yu,Fengshu Fei,Jianting Huang,Chuanlong Guo
RL/BAI nanomicelles (~100 nm) enhance baicalein biocompatibility. • RL/BAI triggers mitochondrial dysfunction and mtDNA release in TNBC cells. • RL/BAI activates cGAS-STING pathway to suppress tumor growth and metastasis. Triple-negative breast cancer (TNBC) remains an intractable malignancy due to the lack of specific therapeutic targets and high metastatic potential. Herein, we fabricated rhamnolipid (RL)-encapsulated baicalein (BAI) nanomicelles (RL/BAI) via a thin-film hydration method. Molecular dynamics (MD) simulations revealed that RL and BAI spontaneously assembled into stable nanomicelles (~100 nm) driven by van der Waals and hydrophobic interactions, achieving high encapsulation efficiency (~85 %) and excellent biocompatibility. In 4T1 cells, RL/BAI nanomicelles enhanced cellular uptake and achieved efficient mitochondrial colocalization, triggering mitochondrial membrane potential (MMP) collapse, excessive mitochondrial reactive oxygen species (mtROS) generation, and mitochondrial DNA (mtDNA) release. These events activated the cGAS-STING pathway, as evidenced by increased phosphorylation of STING, TBK1, and IRF-3, together with upregulation of IFN-γ and NF-κB, ultimately promoting immunogenic cell death. In 4T1 xenograft models, RL/BAI significantly inhibited primary tumor growth and lung metastasis, remodeled the pro-inflammatory tumor microenvironment by upregulating pro-inflammatory cytokines and promoting dendritic cell maturation, with no obvious systemic toxicity. Collectively, RL/BAI nanomicelles exert anti-TNBC effects through mitochondrial damage and cGAS-STING pathway activation, providing a novel natural biosurfactant-based nanomedicine strategy for TNBC treatment.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Xiaobing Yao,Yuan Ruan,Ting Rao,Fangyou Lin,Wenbin Zhang
Prostate cancer is a prevalent immune-cold malignancy in which hypoxia and glutathione (GSH) enrichment hinder redox-dependent therapies and cuproptosis. A hyaluronic-acid–coated copper–manganese Prussian blue nanomedicine (Cu/Mn-PB@HA) was developed to remodel the tumor microenvironment (TME) and enhance mitochondria-associated cuproptosis. The multivalent Cu/Mn centers enable catalase-like O 2 generation, GSH-oxidase–like depletion of GSH, and Fenton-like ·OH production, which together enhance chemodynamic therapy (CDT) and create a favorable window for cuproptosis. In acidic and GSH-rich conditions, copper valence cycling initiates cuproptosis, whereas released Mn 2+ enhances CDT and activates the cGAS–STING pathway, thereby promoting dendritic-cell maturation and cytotoxic T-cell responses. The HA shell enables CD44-mediated enrichment, improving tumor accumulation without compromising biosafety. In vitro , the platform elevates ROS, induces mitochondrial depolarization, downregulates HIF-1α, and modulates cuproptosis-related proteins. Concurrently, immunogenic cell-death markers are elevated together with cGAS–STING signaling. In vivo , preferential tumor accumulation and significant tumor inhibition are achieved with favorable serum biochemistry and hepatic/renal histology. By integrating “oxygenation–desensitization–ROS” chemistry with Mn 2+ - enhanced immune activation, Cu/Mn-PB@HA provides a comprehensive strategy for treating immune-cold solid tumors and serves as a versatile platform for theranostic development.
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CELLULAR SIGNALLING
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2025
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IF 3.7
Suli Chong,Yang Liu,Ziming Bian,Dongxue Hu,Shiqun Guo,Chenfei Dong,Jiayue Zeng,Sairong Fan,Xiaoming Chen
Despite significant advancements in immunotherapy for cancer treatment, its effectiveness in pancreatic ductal adenocarcinoma (PDAC) remains disappointing, which is greatly due to the unique immunosuppressive microenvironment of PDAC. Here, we focus on the involvement of GALNT6 in immune evasion mechanisms in PDAC. Our results reveal a negative relationship between GALNT6 expression and immune cell infiltration in PDAC. Knockdown of GALNT6 enhances PDAC cells sensitivity to cytotoxic T cells and macrophages. Mechanistically, GALNT6-mediated glycosylation blocks the translocation of STING (stimulator of interferon genes) and accelerates its degradation in a cGAS-independent manner, leading to reduced levels of type I interferon (IFN-β) and CCL5 and CXCL10, thus promoting PDAC immune evasion by inhibiting cytotoxic CD8 + T cell and macrophage infiltration. Furthermore, GALNT6 stabilizes PD-L1 by blocking its ubiquitin-proteasome degradation, thereby promoting tumor immune evasion. Notably, the combination of an O-glycosylation inhibitor with PD-1/PD-L1 inhibitors synergistically enhances the anti-cancer immune response. In summary, these findings highlight GALNT6 as a critical player in immune evasion, and targeting GALNT6 could serve as a valuable approach to boost anti-tumor immunity in PDAC patients.
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PHYTOMEDICINE
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2025
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IF 8.3
Yifan Guo,Taiqi Xue,Xiangfei Meng,Pu Yan,Meng Zhang,Qian Zhang,Tongxia Li,Kaifeng Shi,Ning Zhang
Background The cGAS/STING-mediated inflammatory response plays a key role in diabetic kidney disease (DKD) pathogenesis. However, effective anti-inflammatory therapies to halt disease its progression remain unavailable. The Qihuang Yishen (QHYS) formula has been demonstrated to reduce proteinuria and halt the course of DKD. However, the underlying mechanism of QHYS remains unclear. Purpose The purpose of this study was to determine whether QHYS had anti-inflammatory effects on DKD by targeting the cGAS/STING pathway both in vitro and in vivo . Methods In vivo , DKD models were established in KK-Ay mice using a high-fat diet. In vitro , human renal tubular epithelial cells (HK-2) were exposed to high glucose (HG) and palmitic acid (PA) for 24 hours to simulate renal tubular injury. Both experimental settings received interventions with QHYS or canagliflozin (positive control drug). Bioactive components in QHYS-containing serum were characterized by HPLC-ESI/MS. Body weight, random blood glucose, renal function markers, urinary protein levels, renal tubular injury indicators, and renal histological lesions were evaluated. Mitochondrial ultrastructure was analyzed by transmission electron microscopy (TEM). Western blotting quantified mitochondrial proteins TFAM and TOM20. Cell viability was assessed via CCK-8 assay, while ELISA kits measured IL-6 and TNF-α levels in cell supernatant. Quantitative PCR assessed expression of mtDNA and inflammatory mediators (IL-6, TNF-α, IFN-γ and CXCL10 mRNA). For cGAS/STING pathway analysis, key proteins were evaluated through western blotting, immunofluorescence, and immunohistochemistry. Additionally, mtDNA transfection experiments in HK-2 cells elucidated QHYS's regulatory mechanism on this pathway. Results HPLC-ESI/MS identified 32 principal bioactive components in QHYS. In vivo experiments showed that QHYS significantly reduced Scr and UREA levels ( P < 0.05), decreased UACR, 24 h UTP and renal tubular injury markers NAG and NGAL levels ( P < 0.01), and alleviated renal histopathological damage in KK-Ay mice, including glomerular hypertrophy, mesangial matrix expansion, tubular vacuolar degeneration, and tubulointerstitial inflammation. Moreover, QHYS ameliorated mitochondrial structural damage, upregulated the expression of TFAM and TOM20 ( P < 0.05), and suppressed cGAS/STING pathway activation ( P < 0.01). In vitro experiments demonstrated that QHYS alleviated mitochondrial damage ( P < 0.05) and mtDNA leakage ( P < 0.01), and inhibited cGAS/STING signaling and downstream inflammation ( P < 0.05). More importantly, transfecting mtDNA into the cytoplasm to mimic the leakage process demonstrated that QHYS-containing serum directly inhibits cGAS/STING pathway activation ( P < 0.05), and this mechanism also alleviated renal tubular injury in DKD. Conclusion QHYS attenuates renal tubular inflammatory damage via cGAS/STING pathway regulation. This pioneering study provides the first evidence that herbal medicine exerts renal tubule protection through multi-target regulation of innate immune-mediated inflammatory injury in metabolic nephropathy, offering novel scientific evidence for DKD intervention.
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BIOMATERIALS
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2025
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IF 12.9
Shijian Liu,Sijie Shao,Zhe Huang,Panpan Xue,Shuangqian Yan,Mengru Cao,Xuemei Zeng
Aberrant cholesterol accumulation and hypoxia contribute to cancer malignancy by promoting cell survival, enhancing DNA repair pathways, reducing the efficacy of the stimulator of the interferon gene (STING) activation, and creating an immunosuppressive tumor microenvironment. In this study, we developed a manganese-based nanoplatform, termed MnO x ChP, which combines peroxidase-, catalase-, glutathione oxidase-, and NADPH oxidase-like nanozyme activities with cholesterol oxidase (ChOx) to enhance STING activation for effective cancer immunotherapy by modulating cholesterol metabolism and hypoxia. ChOx catalyzes the oxidation of cholesterol and O 2 into H 2 O 2 , depleting cholesterol, which disrupts lipid rafts domains, inhibits DNA damage repair, and increases membrane fluidity. This process amplifies the cytosolic DNA pool, induced by lethal • OH from the Fenton-like reaction, thereby strengthening STING activation mediated by Mn 2+ . Additionally, the multiple enzyme-like activities of MnO x overcome the tumor's antioxidant defense system and alleviate hypoxia, further enhancing • OH-induced lethality and cholesterol oxidation. Cholesterol depletion also inhibits the PD-1/PD-L1 axis, mitigating CD8 + T cells exhaustion. The MnO x ChP nanoplatform induces potent immunogenic cell death, demonstrating significant immunotherapeutic efficacy in both abscopal and metastasis mouse models. This strategy amplifies STING activation and expands the potential of cholesterol metabolism modulation-based immunotherapy.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Shousheng Liu,Haiping Zhang,Ronghuan Du,Xi Gao,Tianren Wang,Wenping Qin,Dan Sun,Hui Liang,Peng Wang
Emerging research evidence has established the critical role of inflammatory cascades in the development and progression of alcoholic liver injury with hepatocellular death serving as a principal driver. Notably, the dysregulated interplay between mitochondrial homeostasis and pyroptosis is primarily responsible for the alcohol-induced aberrant liver immune microenvironment, characterized by nonresolving inflammation. Given the considerable limitations in the current treatment for alcoholic steatohepatitis (ASH), it is imperative to explore targeted nutritional interventions as alternative therapies. Here, we established an ASH model with C57BL/6J mice and demonstrated that astaxanthin (AST) administration significantly protected against alcohol-induced inflammatory liver injury through dual mechanisms: 1) suppression of hepatocyte pyroptosis by inhibiting the NLRP-3/Caspase/GSDMD signaling axis and 2) mitigation of mitochondrial dysfunction evidenced by structural membrane integrity restoration and redox homeostasis rebalancing. Mechanistically, AST intervention impeded the cytoplasmic translocation of mitochondrial DNA (mtDNA), thereby concurrently inhibiting AIM2 inflammasome activation and cGAS/STING signaling. In vitro studies further confirmed dose-dependent attenuation of alcohol-induced hepatotoxicity by AST, marked by reduced pyroptotic cell death and diminished proinflammatory cytokine secretion (IL-1β, IL-18). Mitochondrial protection was further evidenced through restored membrane potential (ΔΨm), decreased cytoplasmic Cytochrome C release, and attenuated mtDNA leakage. Moreover, we identified a novel molecular interaction, wherein AST competitively binds lipid-binding motifs within the β1−β2 loop of the GSDMD-N-terminal domain, potentially interfering with pyroptotic pore formation. Further overexpression experiments confirmed the improvement effect of AST on pyroptosis induced by GSDMD-N pore formation. Concurrently, AST exhibited potent antioxidant effects against alcohol-induced cardiolipin peroxidation, suggesting dual therapeutic modalities targeting both pyroptotic execution and mitochondrial membrane stabilization. Collectively, our findings identify AST as a promising candidate for therapeutic interventions against alcoholic inflammatory liver injury through coordinated modulation of the pyroptosis-mitochondrial homeostasis crosstalk, offering novel insights into nutritional intervention strategies for alcohol-related liver pathologies.
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JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Yanming Xia,Lixin Hu,Yuhan Hu,Shihao Wang,Qingqing Xiong,Xiaohu Wang,Yiqun Li,Lifang Yin,Jian Wang,Suxin Li
The stimulator of interferon genes (STING) has emerged as a promising target for cancer immunotherapy. However, STING agonists alone have demonstrated limited clinical success. Indoleamine 2,3-dioxygenase 1 (IDO1) has been implicated as a key resistance mechanism that undermines the antitumor effects of STING activation, yet the cell-type-specific roles and the combined impact of STING and IDO1 on tumor immune orchestration remain poorly understood. In this study, we report that a co-delivery nanosystem of STING agonists and IDO1 inhibitors, rather than their simple combination, yields synergistic antitumor responses. This nanomedicine exhibits tropism toward myeloid cell populations in vivo , particularly dendritic cells (DCs), and facilitates pH-responsive cytosolic delivery of both agents. As a result, it enhances antigen cross-presentation, DC maturation, and cytokine secretion, driving effective priming of cytotoxic T lymphocytes. Compared to monotherapies or physical nanoparticle combinations of STING agonists and IDO1 inhibitors, this two-in-one nanomedicine significantly suppresses tumor growth and confers a survival benefit. Depletion of STING in the host ( Tmem173 −/− mice) or deficiency in type I conventional DCs (cDC1s, Batf3 −/− mice) abolishes therapeutic efficacy, whereas depletion of STING in tumor cells exerts minimal impact. A bone marrow chimera experiment further supports the STING-cDC1 dependence. Its capability to overcome tumor resistance and the underlying mechanism were further investigated in a well-established tumor model. Our findings highlight the cooperative role of STING activation and IDO1 blockade within cDC1s and introduce an integrated drug delivery system to combat immune tolerance in cancer therapy.
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Bioactive Materials
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2021
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IF 14.593
Jiaxin Chen,Haifeng Zhu,Yutao Zhu,Chenchen Zhao,Shengyu Wang,Yixin Zheng,Ziang Xie,Yang Jin,Honghai Song,Linjun Yang,Jin Zhang,Jiayong Dai,Zhijun Hu,Huaiyu Wang
Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING–NF–κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system ( [email protected] gel ) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the [email protected] gel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.
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International Journal of Nanomedicine
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2023
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IF 8
Boyi Yu,Xuanyi Lu,Xianglong Feng,Ting Zhao,Jiaxin Li,Yudie Lu,Fei Ye,Xiongxiong Liu,Xiaogang Zheng,Zheyu Shen,Xiaodong Jin,Weiqiang Chen,Qiang Li
Introduction Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.Methods 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization.Results GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway.Discussion Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Kehong Dong,Yuxuan Sun,Xintao Gao,Jing Wang,Xiaochen Wu,Chuanlong Guo
Excessive acetaminophen (APAP) is the main cause of drug-induced acute liver failure, and the pathogenesis has not been elucidated and there is a lack of effective drugs. Hesperidin (Hes), a rich flavanone in citrus peel with excellent biological activities, is a potential agent for treatment liver injury. Due to poor water solubility of Hes, this study prepared mixed micelles using polyvinyl pyrrolidone (PVP K17) and poloxamer 188, and encapsulated Hes (Hes-MMs). The results showed that Hes-MMs exhibited a uniform spherical shape with a particle size of 66.80 ± 0.83 nm, and Hes-MMs significantly improved the dispersibility, antioxidant activity , and cellular uptake of Hes. In vitro results showed that Hes-MMs protected the proliferation inhibition of HepG2 cells induced by APAP, inhibited the production of reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP) induced by APAP. Furthermore, Hes-MMs exerted liver protective effects by inhibiting APAP induced mtDNA release and activating the cGAS-STING pathway. In vivo results demonstrated that Hes-MMs showed protective and therapeutic effects on APAP induced liver injury, and their mechanisms were related to the mtDNA-cGAS-STING signaling pathway . In summary, our study demonstrated that the mtDNA-cGAS-STING pathway was involved in APAP induced acute liver injury, and Hes-MMs might be a potential therapeutic agent for treating APAP induced acute liver injury.
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Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Zhiqiang Zhang,Li Wang,Xia Ma,Hui Wang
A series of biodegradable nanoparticle-based drug delivery systems have been designed utilizing poly(β-amino ester)-guanidine-phenylboronic acid (PBAE-G) polymers. In this study, a novel Lentinan-Functionalized PBAE-G-nanodiamond system was developed to carry ovalbumin (LNT-PBAE-G-ND@OVA). The impact of this drug delivery system on the activation and maturation of macrophages was then assessed. Furthermore, LNT-PBAE-G-ND@OVA induced potent antibody response and showed no obvious toxicity in vitro and in vivo . Moreover, treatment with LNT-PBAE-G-ND@OVA was sufficient to alter the expression of genes associated with the cGAS-STING pathway, and the LNT-PBAE-G-ND@OVA induced upregulation of costimulatory molecules. LNT-PBAE-G-ND@OVA treatment was sufficient to induce macrophage activation through a complex mechanism in which cGAS-STING signaling plays an integral role.
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