JOURNAL OF NANOBIOTECHNOLOGY
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2025
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IF 12.6
Wei-Hua Zhang,Lei Chen,Lin Gao,Ye-Ming Wu,Zhi-Cheng Jin,Jian-Jian Chen,Yan-Li An,Gao-Jun Teng
Incomplete radiofrequency ablation (iRFA) often results in tumor recurrence and therapeutic resistance, presenting significant clinical challenges. Tumors subjected to sublethal thermal injury activate the HSP70/ NQO1 antioxidant pathway and secrete elevated levels of CCL2, which recruits macrophages and fosters an immunosuppressive tumor microenvironment. To address these issues, this study engineered copper-doped ZIF-8 nanoparticles that co-deliver the hypoxia-activated prodrug TH-302 and the NQO1-targeting quinone β-lapachone, encapsulated within genetically engineered M1 macrophage membranes overexpressing CCR2 (CCR2-M). This innovative CCR2-M biomimetic coating enhances tumor targeting by sequestering excess CCL2, effectively reducing pro-tumoral macrophage infiltration. β-lapachone selectively targets NQO1-overexpressing tumor cells, elevating intracellular H 2 O 2 levels, while copper-doped ZIF-8 catalyzes Fenton-like reactions to generate cytotoxic hydroxyl radicals. Simultaneously, TH-302, responsive to hypoxia, complements β-lapachone by inducing cell death in hypoxic regions, thereby mitigating β-lapachone’s oxygen dependence. This synergistic ROS burst effectively suppressing tumor growth, activating the cGAS-STING pathway and enhancing tumor antigen presentation. This synergistic ROS burst effectively suppresses tumor growth, activates the cGAS-STING pathway and enhances tumor antigen presentation. This cascade recruits dendritic cells and cytotoxic CD8 + T cells, ultimately reversing the immunosuppressive microenvironment induced by iRFA. No drug-related toxicity was observed. Thus, this rationally designed nanotherapeutic strategy significantly curtails residual tumor growth and offers a promising immunomodulatory approach to overcoming therapeutic resistance in cancer treatment after iRFA.
研究领域:
纳米医学
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癌症免疫治疗
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肿瘤微环境
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仿生纳米材料
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放射肿瘤学
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高影响因子
Advanced Science
·
2026
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IF 14.1
Yuelan Wu,Wenbo Geng,Qinjin Dai,Wanyun Zhang,Yuxian Lai,Pei Zhang,Chunjiang Zhou,Yinuo Wang,Qingfeng Cao,Xiang Luo,Yujie Lai,Changwei Huang,Peizeng Yang
Autoimmune uveitis is a sight-threatening inflammatory disease in which the cGAS-STING signaling pathway exacerbates inflammation by recognizing excessive cell-free DNA (cfDNA). However, conventional cfDNA scavengers have limited blood-retinal barrier penetration, and monotherapies cannot control the complex inflammatory network. Herein, we developed a cationic poly(disulfide)-drug nanoplatform (LA/DexP), which self-assembled via salt bridge interactions and aggregation-induced polymerization between a guanidyl-functionalized lipoic acid derivative (LA) and dexamethasone phosphate (DexP). This platform is designed to synergistically inhibit the cGAS-STING pathway and achieve efficient intraocular drug delivery. LA/DexP functioned as an efficient scavenger of cfDNA through electrostatic interaction, thereby inhibiting cGAS-STING overactivation. Meanwhile, it leveraged thiol-disulfide exchange to enhance blood-retinal barrier penetration, achieving a 5.09-fold higher apparent permeability coefficient than free DexP, and exhibited ROS-responsive drug release. In an experimental autoimmune uveitis mouse model, LA/DexP treatment significantly reduced cfDNA levels and inhibited cGAS-STING signaling. It also downregulated pro-inflammatory cytokine expression, promoted macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, and rebalanced Th1/Th17-Treg cell subsets. These combined effects effectively inhibited uveitis severity. In summary, this study establishes a highly barrier-permeable nanoplatform that synergistically integrates drug delivery with cGAS-STING pathway inhibition, offering a promising therapeutic strategy for autoimmune uveitis.
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高影响因子
Discover Nano
·
2026
·Vol. 21
·期 1
·415
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IF 6.7
Long Lin,Zhang Yexi,Xiao Jun,Zang Jianhua
Purpose To fabricate hesperetin-loaded fucoidan-selenium (Hes/Fu-Se) nanoparticles (NPs) for alleviating cisplatin-induced acute kidney injury (AKI), overcoming hesperetin’s low solubility and bioavailability and boosting antioxidant and anti-inflammatory efficacy. Methods Hes/Fu-Se NPs were prepared by encapsulating hesperetin within fucoidan, and then functionalized selenium (Se) NPs. Nanoparticle physicochemical properties and antioxidant activity (FRAP, ABTS) were characterized. Cisplatin-stimulated HK-2 cells were used for in vitro detection of cell viability, apoptosis, ROS accumulation, mitochondrial function and cGAS-STING signaling. A cisplatin-induced AKI mouse model was adopted to test renal biochemical indexes, renal histopathology and renal injury-related protein expression. Results Synthesized Hes/Fu-Se NPs exhibited uniform particle size, superior aqueous solubility and potent antioxidant activity. In vitro, the NPs restored HK-2 cell viability, mitigated apoptosis and ROS overproduction, and inhibited DNA damage and cGAS-STING cascade activation. In vivo, Hes/Fu-Se markedly reduced serum BUN and CRE, alleviated renal histological lesions and inflammatory infiltration, and downregulated the expression of cGAS, STING, γH2AX and TNF-α in kidney tissues. Conclusions Hes/Fu-Se NPs relieve cisplatin-triggered AKI via amplified antioxidation, DNA damage restoration and cGAS-STING pathway suppression. This nanoformulation provides a promising nephroprotective strategy against chemotherapy-related renal toxicity for clinical translation. Graphical abstract
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Biosensors-Basel
·
2026
·Vol. 16
·期 5
·261
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IF 6.2
Ziyi Li,Yingxin Tian,Gefei Ren,Yingshu Guo
The overexpression of hypoxia-inducible factor-1α (HIF-1α) suppresses STING signaling and modulates lipid metabolism in tumor cells, leading to abnormal lipid droplet (LD) accumulation. Herein, we constructed a manganese dioxide (MnO2)-based nanomotor (HMIP@A). HMIP@A depletes intracellular hydrogen peroxide (H2O2) and glutathione (GSH) to generate oxygen (O2), reactive oxygen species (ROS), and manganese (Mn2+). A dual strategy of “oxygen supplementation” and “small-molecule inhibition” synergistically downregulates HIF-1α, thereby suppressing LD biogenesis. This process sensitizes tumor cells to ROS, leading to severe DNA damage. Released Mn2+and damaged DNA synergistically activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. In vitro, HMIP@A markedly increases ROS production, lipid peroxidation (LPO), and DNA damage, thereby inducing tumor cell death, immunogenic cell death (ICD), and dendritic cell (DC) maturation. Furthermore, HMIP@A exhibits excellent penetration in tumor spheroids. Overall, this study provides a theoretical basis for the design of nanomedicines through a strategy integrating metabolic intervention, oxidative damage sensitization, and immune activation.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Yu Jiang,Yaowu Zhang,Jingqi Hou,Heng Liu,Xianyu Dai,Yuchuan Hou
Characterizing the tumor immune microenvironment (TIME) to explore potential therapeutic targets is fundamental to advancing precision tumor immunotherapy. However, the immunosuppressive nature of “cold” tumors, notably prostate cancer, poses a significant barrier to immunotherapy, demanding new approaches to simultaneously reinvigorate anti-tumor immunity and modulate the molecular drivers of immune evasion. Here, we identified VSIG4 as a key regulator of prostate tumor-resident macrophage fate through single-cell sequencing analysis. Meanwhile, a shikonin (Shik)-mediated downregulation of VSIG4 in macrophages is verified, potentially attenuating its immunosuppressive effects. Building on these findings, cytosine guanine dinucleotide (CpG) oligodeoxynucleotide (ODN)-modified manganese (Mn)-Shik metal-polyphenol network nanodrugs (Mn/Shik@CpG NDs) are designed to reverse the “cold” immune environment of prostate tumor. In this scenario, Mn/Shik@CpG NDs release monomeric components under the stimulation of acidic and glutathione-rich tumor microenvironment (TME), thus exerting their immunomodulatory effects synergistically. Since the released Shik can induce DNA damage by necroptosis promoting reactive oxygen species production, cGAS-STING signaling pathway is initiated, which further activates interferon production in the TME. In addition, the necroptosis of Shik initiates immunogenic cell death, further activating innate immunity and promoting adaptive immune responses. Mn 2+ is a cGAS-STING sensitizer, which amplifies the intratumoral interferon response. As an immune adjuvant, CpG ODN effectively promotes the maturation of dendritic cells, as well as the helper T cell differentiation and pro-inflammatory cytokine secretion, thus activating both innate and adaptive immunity. In vivo studies suggest that Shik-mediated VSIG4 downregulation, combined with innate and adaptive immune activation, remodels the TIME to evoke a significant anti-tumor response. Furthermore, transcriptomic analysis of rechallenged tumors indicated this durable protection was driven by a genuine immune memory response, revealing a gene signature of T cell activation and immune reprogramming. Collectively, beyond presenting a novel therapeutic candidate for converting immunologically “cold” tumors into “hot” ones, our work validates a data-guided design pipeline, offering a conceptual blueprint to inform the precise engineering of future nanodrugs.
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高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2026
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IF 4.5
Song Hu,Linghui Kong,Mo Chen,Cheng Teng,Ying Zhao,Xiaohong Yuan,Shunv Cai,Xiaoyan Zhu,Pingbo Xu
The docetaxel-carboplatin (TCb) combination is a widely used neoadjuvant chemotherapy regimen, yet its clinical application is frequently accompanied by hepatotoxicity and drug-induced liver injury (DILI). However, the underlying molecular mechanisms remain incompletely understood. This study investigates the role of cGAS-STING-mediated autophagy in TCb-induced DILI. A TCb-induced DILI mouse model is established by intraperitoneal administration of docetaxel (10 mg/kg) and carboplatin (50 mg/kg) once weekly for two weeks, alongside an in vitro AML12 hepatocyte model (docetaxel 20 μM + carboplatin 100 μM). Liver injury, apoptosis, autophagy, and cGAS-STING signaling are evaluated using histopathological staining, biochemical assays, RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. TCb treatment induces significant liver injury, as evidenced by elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL), histopathological damage, and increased collagen deposition. TCb markedly promotes hepatocyte apoptosis, characterized by increased expression of Bcl-2 associated X protein (BAX) and decreased expression of Bcl-2. Concomitantly, TCb suppresses basal autophagy, as indicated by p62 accumulation, reduced Beclin-1 expression, decreased LC3-II/I ratio, and diminished autophagosome formation. Mechanistically, TCb robustly activates the cGAS-STING pathway, accompanied by enhanced phosphorylation of TBK1 and IRF3. Notably, pharmacological inhibition of STING with C-176 or siRNA-mediated STING knockdown restores autophagic flux and significantly attenuates TCb-induced apoptosis. Collectively, these findings suggest that sustained activation of the cGAS-STING pathway contributes to TCb-induced DILI by impairing autophagic homeostasis and promoting hepatocyte apoptosis. Targeting cGAS-STING-mediated autophagy represents a potential therapeutic strategy for preventing chemotherapy-associated hepatotoxicity.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jinjin Liu,Dan Wang,Shuya Wang,Xiaojing Shi,Tingli Xiong,Yebin Lu,Jianbo Yang,Wei Wei,Xuejun Gong,Qiong Huang,Liandong Ji,Kelong Ai
Acute pancreatitis (AP), a potentially fatal disorder driven by macrophage-associated inflammation, involves mitochondrial reactive oxygen species (ROS) overproduction with pancreatic acinar cells (PACs). This ROS surge damages mitochondria, causing mitochondrial DNA (mt-DNA) leakage and PACs apoptosis. Released mt-DNA then activates the pro-inflammatory cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in macrophages, exacerbating disease progression. Critically, while scavenging mitochondrial ROS can halt this cycle, existing mitochondria-targeted drugs fail to penetrate the damaged blood-pancreas barrier (BPB). To overcome this limitation, we developed MTP, a novel dual-targeting nanomedicine synthesized from tannic acid, dopamine, and molybdenum oxides. MTP uniquely achieves dual targeting: actively homing to injured BPB and specifically accumulating within PACs mitochondria. This enables robust mitochondrial ROS scavenging, which protects mitochondrial integrity, reduces mt-DNA release, inhibits PACs apoptosis, and crucially blocks mt-DNA-induced cGAS-STING activation in macrophages, thereby suppressing their pro-inflammatory M1 polarization. By simultaneously interrupting both ROS-mediated PACs damage and macrophage-driven inflammation via this dual-targeting strategy, MTP effectively mitigates AP progression, establishing a breakthrough therapeutic approach.
研究领域:
纳米医学
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免疫学
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炎症
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线粒体生物学
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活性氧（ROS）
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信号转导
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高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Ling Yu,Fengkai Qiu,Yumin Hu,Tingting Liao,Mengqian Zhai,Ronghua Wu,Qianhui He,Huilin Hu,Shuiwei Xia,Junguo Hui,Zufei Wang,Yang Yang,Rongfang Qiu,Minjiang Chen,Weiqian Chen,Jianfei Tu,Jiansong Ji,Chenying Lu
Because of the high incidence and mortality of cancer, there is an urgent need for more effective tumor diagnostic imaging and treatment strategies. Single-molecule therapeutics have emerged as a promising strategy to address the limitations of independent imaging and therapeutic modalities, thereby significantly reducing adverse side effects for patients. For the first time, we successfully synthesized NaGd(MoO4)2 nanoparticles via a homogeneous precipitation method in polyol media, which serve as a single-molecule agent for MRI imaging and metallic immunotherapy. With the addition of iRGD, we obtained iRGD-NaGd(MoO4)2. The iRGD-NaGd(MoO4)2 nanoparticles exhibit excellent tumor-targeting capability and significantly enhance T1-weighted MRI contrast with a longitudinal relaxivity of 4.95 mM–1 s–1. In terms of antitumor immunotherapy, iRGD-NaGd(MoO4)2 not only directly activates the cGAS-STING pathway but also induces ferroptosis in tumor cells, resulting in the generation of aberrant dsDNA and thereby indirectly activating the STING pathway. The dual pathway elicits a tumor-specific immune response, plays a significant role in promoting the maturation of DC cells, activates DC and T cells to secrete high levels of TNF-α, IL-6 and other cytokines, and regulates the polarization of macrophages from M2 phenotype to M1 phenotype. This mechanism significantly suppresses tumor growth. Beyond the metallic immunotherapy induced by Mn2+, Zn2+, and Co2+, this study provides robust validation of MoO42– as an effective cGAS-STING agonist. Moreover, this study achieved the synergy of multiple disciplines including biomaterials, tumor immunotherapy and medical imaging. This not only promotes the innovative integration in various fields, but also provides new treatment strategies and imaging tools for cancer treatment, which has important clinical application prospects.
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高影响因子
International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Teng Xiao,Fanghong Wang,Ye Li,Gaoyang Lin,Xiaochen Wu
Acute kidney injury (AKI) is a severe clinical condition with high morbidity and mortality, often triggered by nephrotoxic drugs like cisplatin. The cGAS/STING pathway, activated by DNA damage, plays a critical role in cisplatin-induced AKI. This study explores the potential of phloretin-loaded selenium nanoparticles (Phl/HS15-Se) as a therapeutic strategy to mitigate cisplatin-induced nephrotoxicity. Phloretin, a natural flavonoid with antioxidant properties, was encapsulated in polyethylene glycol (15)-hydroxy stearate (HS15) micelles and combined with selenium nanoparticles to enhance its renal protective effects. The in vitro and in vivo experiments demonstrated that Phl/HS15-Se significantly reduced oxidative stress, DNA damage, and inflammation by inhibiting the cGAS/STING pathway. In a cisplatin-induced AKI mouse model, Phl/HS15-Se alleviated renal pathological injury, improved renal function, and reduced the expression of inflammatory markers. This study provides a promising nanomedicine approach for the treatment of cisplatin-induced AKI by targeting the cGAS/STING pathway.
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高影响因子
Materials Today Bio
·
2026
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IF 10.2
Henan Xu,Yuxin Jiang,Ruohao Zhang,Daguang Wang,Jing Feng,Hongjie Zhang
Chemotherapy and photothermal therapy (PTT) have made prominent progress in the treatment of gastric cancer. However, the poor targeting of chemotherapeutic drugs and the thermotolerance or collateral damage induced by PTT lead to suboptimal therapeutic outcomes. To address these issues, we developed a mild PTT (mPTT) nanoparticle based on mesoporous polydopamine (MPDA), loaded with oxaliplatin (OXP) and manganese dioxide (MnO 2 ), and coated with tumor cell membranes to enhance the targeting capability. On one hand, this nanoparticle disrupts glycolysis by inhibiting hypoxia-inducible factor (HIF), while suppressing heat shock proteins (HSP) to mitigate tumor "thermotolerance." On the other hand, the reactive oxygen species (ROS) generated by the MnO 2 -mediated Fenton-like reaction, OXP, and mPTT also induce immunogenic cell death (ICD) to boost adaptive immunity, as well as activate the cGAS-STING pathway through tumor DNA damage to reinforce innate immunity. The activation of both adaptive and innate immune responses triggers a potent antitumor immune reaction, which, combined with chemotherapy and enhanced mPTT, significantly suppresses tumor growth, metastasis and recurrence. This strategy not only enhances the targeting of chemotherapeutic drugs but also provides new possibilities for expanding the field of immunotherapy in gastric cancer by regulating tumor metabolism and enhancing mPTT.
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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
Asian Pacific Journal of Tropical Biomedicine
·
2026
·Vol. 16
·期 6
·225
·
IF 1.9
Zhang Rui,Zhou Yang,Xiao Ting,Gu Yan
Objective: To evaluate the effect of isorhamnetin on diabetic kidney disease and elucidate its underlying mechanisms. Methods: A high glucose-stimulated mouse podocyte (MPC-5) model was employed to evaluate the effects of isorhamnetin on podocyte injury, secretion of inflammatory cytokines, NLRP3 inflammasome activation, pyroptosis, mitochondrial function, cytosolic release of mtDNA, and activation of the cGAS-STING signaling pathway. Nigericin (an NLRP3 activator) and siRNA were used in combination to clarify the regulatory relationships between these pathways. Furthermore, a mouse model of diabetic kidney disease was established and treated with isorhamnetin via intragastric administration. Blood glucose and renal function parameters were measured, renal histopathological changes were examined, and alterations in podocyte marker proteins, inflammasome activation, pyroptosis, mitochondrial damage, and the cGAS-STING pathway in kidney tissues were analyzed. Results: Isorhamnetin alleviated high glucose-induced abnormalities in podocyte marker proteins and cellular injury. It also inhibited NLRP3 inflammasome activation, thereby attenuating pyroptosis. Furthermore, isorhamnetin stabilized mitochondrial membrane potential, decreased mitochondrial ROS production, suppressed excessive opening of the mitochondrial permeability transition pore, alleviated mitochondrial damage, and reduced cytosolic mtDNA release, which in turn suppressed activation of the cGAS-STING pathway. Knockdown of STING inhibited high glucose-induced NLRP3-dependent pyroptosis. Consistently, isorhamnetin improved renal function in mice with diabetic kidney disease, attenuated glomerulosclerosis and fibrosis, and markedly suppressed mitochondrial damage, mtDNA leakage, cGAS-STING activation, and NLRP3-mediated pyroptosis and inflammatory responses in renal tissues. Conclusions: Isorhamnetin treatment attenuates diabetic kidney disease by improving mitochondrial homeostasis and inhibiting the cGAS-STING/NLRP3 inflammasome pathway.
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高影响因子
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