ADVANCED MATERIALS
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2026
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IF 29.1
Minglu Tang,Chenwei Jiang,Mingmei Guo,Qi Chen,Qi Shang,Lin Xiong,Wen Zhang,Liang Dong,Qi Yue,Xihui Gao,Feihu Wang
Personalized vaccines represent a promising approach for cancer treatment by eliciting tumor-specific immune responses. However, their development faces persistent challenges, including the laborious and costly process of neoantigen identification, which substantially delays vaccine production. Moreover, conventional platforms suffer from rapid systemic clearance and inefficient delivery to antigen-presenting cells (APCs), leading to only transient and weak immune activation. Here, we report a STING-agonist-integrated hydrogel system designed for localized delivery of tumor-derived extracellular vesicles (TEVs) to achieve robust and durable antitumor immunity. Upon subcutaneous administration, the in situ formed hydrogel vaccine acts as a depot for antigen-rich TEVs and STING agonists. We demonstrate that this vaccine promotes dendritic cells (DCs) recruitment and establishes an immune-permissive niche through spatiotemporal control over antigen-adjuvant distribution and prolonged APC-antigen engagement. Within this niche, DCs efficiently internalize and process TEVs under STING-mediated activation. These matured DCs subsequently migrate to draining lymph nodes, where they initiate potent and sustained tumor-specific T-cell responses. Our results show that rapidly producible personalized vaccines derived from melanoma TEVs effectively inhibit tumor growth. In a postoperative breast cancer model, patient-tailored TEV vaccines also markedly prevent tumor recurrence and metastasis. This readily customizable platform represents a robust and translatable strategy for personalized cancer immunotherapy.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Qingqing Huang,Nana Feng,Xianghui Cao,Jian Xiao,Qiushi Li,Biyu Zhou,Yating Bai,Yu Zhao,Zhanzhan Zhang,Yang Liu
Breast cancer generally does not respond to immunotherapy due to its inherently low immunogenicity and insufficient coordination between innate and adaptive immune responses. Here, we demonstrated that concurrent activation of immunogenic cell death (ICD) and the cyclic GMP–AMP synthase-stimulator of interferon genes (cGAS–STING) pathway synergistically amplifies antitumor immunity by promoting dendritic cell maturation, co-stimulatory signaling, and T cell priming. Building on these mechanistic insights, we designed a nanoparticle-based immunomodulator (nanoIM) that integrates a serum albumin-metal core with an endoplasmic reticulum (ER)-targeting polymer shell. Within the tumor microenvironment (TME), nanoIM induces ER stress-mediated ICD and simultaneously releases Mn 2+ or Zn 2+ ions to activate the cGAS–STING pathway, thereby bridging innate and adaptive immune activation. Systemic administration of nanoIM in breast cancer-bearing mice elicited potent T cell infiltration, robust tumor regression, prolonged survival, and effective prevention of metastasis and recurrence. This study uncovers the molecular crosstalk between ICD and cGAS–STING signaling and establishes a nanomaterial-based strategy for durable and systemic immune activation in breast cancer immunotherapy.
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Hongyu Yang,Yuelin Zhao,Sen Mu,Siqi Wang,Aiyang Tong,Dongkai Wang,Jiajia Jia,Ji Li
HA@CZ enables acid-responsive local Ca 2+ /Zn 2+ ion therapy. • Zn 2+ impairs Ca 2+ extrusion and drives sustained Ca 2+ overload. • Dual-ion stress induces caspase-1/GSDMD and caspase-3/GSDME pyroptosis. • HA@CZ cascade-induces pyroptosis and activates the STING pathway. • Local HA@CZ treatment sensitizes 4 T1 tumors to PD-1 blockade. Triple-negative breast cancer responds poorly to immune checkpoint blockade, partly because of insufficient tumor-local immune priming. Controlled delivery of bioactive ions offers an opportunity to induce inflammatory tumor cell death while limiting nonspecific systemic exposure. Here, we developed hyaluronic acid-modified, zinc containing calcium carbonate nanoparticles (HA@CZ) for acid-responsive synchronized Ca 2+ /Zn 2+ delivery. HA@CZ remained colloidally stable under physiological conditions but released Ca 2+ and Zn 2+ more rapidly under tumor relevant acidic conditions. HA@CZ markedly promoted intracellular Ca 2+ /Zn 2+ accumulation, induced mitochondrial dysfunction, and triggered gasdermin dependent pyroptosis through the caspase-1/GSDMD and caspase-3/GSDME axes. Mechanistically, the key distinction of HA@CZ does not lie in Ca 2+ overload alone, but in converting Ca 2+ overload from a direct ion burden process into a Zn 2+ initiated Ca 2+ homeostasis collapse mechanism. Zn 2+ impaired mitochondrial energy metabolism and ATP dependent Ca 2+ extrusion, thereby lowering the threshold for sustained Ca 2+ overload after synchronized ion release. The resulting dual ion stress promoted mitochondrial deoxyribonucleic acid leakage and activated cyclic GMP–AMP synthase stimulator of interferon genes signaling, thereby coupling tumor cell pyroptosis with endogenous deoxyribonucleic acid sensing activation. In syngeneic 4 T1 tumor models, HA@CZ suppressed tumor growth after both systemic and local administration, promoted dendritic cell maturation and CD8 + T-cell infiltration, and remodeled the tumor immune microenvironment toward a pro-inflammatory phenotype. Intratumoral studies confirmed its intrinsic therapeutic superiority over free CaCO₃, Zn 2+ , and their physical mixture, while combination with anti-PD-1 therapy enhanced control of both primary and distant tumors. Furthermore, tumor re-challenge experiments demonstrated that HA@CZ induced durable antitumor immune memory. These findings establish HA@CZ as a controlled-release ion nanotherapeutic that couples synchronized Ca 2+ and Zn 2+ delivery to pyroptosis associated immune activation and checkpoint blockade sensitization. Download: Download high-res image (150KB) Download: Download full-size image
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Manqing Zhang,Yufei Lan,Qu Yue,Jinjun He,Lei Li,Huan Zhang,Yaoyuan Dong,Yuankai Wang,Jiankun Lu,Zhijie Lu,Feiyunduo Hao,Sui Chen,Yixiao Jiang,Chao Zhang,Yan Zhao,Hongbo Guo
Alzheimer's disease (AD) pathological progression is intimately linked to microglial inflammatory activation mediated by the cGAS-STING pathway. Small interfering RNA targeting STING (siSTING) is a precise therapeutic to silence STING and interfere with this pathway, but its clinical translation is severely limited by serum nuclease degradation, inadequate blood-brain barrier (BBB) penetration, and suboptimal targeting. We constructed a lock-equipped six-helix DNA bundle for siSTING delivery. Prior to reaching AD lesions, siSTING was efficiently sequestered within the DNA bundle, ensuring its structural integrity; upon arrival at the lesion site, the carrier undergoes a conformational change in response to the high expression of CD64, thereby triggering the controlled release of encapsulated siSTING. Functional assessments showed this system significantly suppressed cGAS-STING activation, reduced cerebral Aβ plaque deposition, and promoted microglial polarization from M1 (proinflammatory) to M2 (anti-inflammatory). These effects ameliorated memory and learning deficits in AD model mice via enhanced neuroprotection, offering a novel platform for precise targeted therapy of AD.
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 13.2
TingTing Yu,Yuanyuan Li,Ju Zhu,Yihua Sun,Zhendong Li,Li Liang,Yangyang Zhu,Tiantian Dong,Fang Nie
As a non-invasive treatment method, sonodynamic therapy (SDT) has been proven to enhance immune system activity by inducing the generation of reactive oxygen species (ROS). However, the efficacy is constrained by the hypoxic tumor microenvironment (TME) and their intrinsic antioxidant defense mechanisms. To overcome these challenges, we have developed a manganese-based nanoplatform named HMAS@MH, which is responsive to both ultrasound and TME. This nanoplatform utilizes hollow mesoporous manganese dioxide (HM) as a carrier, loaded with oxygen-independent alkyl radical generator AIPH and siNrf2, and coated with hyaluronic acid (HA)-modified erythrocyte membrane (eM). After systemic administration, HMAS@MH preferentially accumulates in tumor regions, benefiting from the extended circulation time afforded by the eM camouflage and the active targeting ability conferred by HA. Under dual stimulation from exogenous ultrasound irradiation and endogenous conditions of low pH and high glutathione (GSH) levels, HMAS@MH decomposes to generate alkyl and hydroxyl radicals, resulting in the accumulation of cytoplasmic double-stranded DNA (dsDNA). Additionally, siNrf2 and Mn 2+ significantly blocks the neutralization of free radicals by inhibiting the antioxidant defense system and depleting GSH. As a non-cyclic dinucleotide stimulator of interferon genes (STING) agonist, Mn 2+ significantly enhances the sensitivity of cyclic GMP-AMP synthase (cGAS) protein to dsDNA, thereby activating the cGAS-STING pathway and triggering robust anti-tumor immune responses. In conclusion, this sonochemical therapy, combined with Nrf2 silencing, amplifies oxidative damage in tumor cells and boosts anti-tumor immunity, resulting in significant tumor suppression.
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Materials Today Bio
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2025
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IF 10.2
Jia Li,Yangbo Xu,Congrui Zhao,Xiaoyu Chen,Chuchu Xu,Chuan Zhou,Hui Wang,Antian Xu,Fuming He
The innate immune response to bone biomaterials critically regulates osteogenesis, yet the molecular mechanisms governing neutrophil-macrophage crosstalk remain poorly understood. Building on our discovery of neutrophil involvement in bone regeneration, we investigated the E3 ubiquitin ligase-Tripartite motif containing protein 30a(TRIM30a) as a potential orchestrator of inflammatory resolution and osseointegration. Through integrated multi-omics analysis of pro-osteogenic versus non-osteogenic metallic implants, we identified TRIM30a as a key regulator. Using conditional knockout mice (whole-body, neutrophil-specific, and macrophage-specific TRIM30a deficiency) combined with NETosis assays and inflammatory signaling profiling, we systematically evaluated TRIM30a's role on NETosis/cGAS-STING axis in bone regeneration, with pharmacological validation using DNase I in murine femoral implant models. TRIM30a expression is positively correlated with the osteogenic ability of pro-osteogenic implants. Mechanistically, TRIM30a suppressed NF-κB/NLRP3 in neutrophils, while synergizing with NET-derived dsDNA to modulate cGAS-STING signaling in macrophages, achieving balanced cytokine production. Therapeutic intervention with DNase I rescued bone formation in TRIM30a-deficient mice, confirming the pathway's clinical relevance. Our work establishes TRIM30a as a master regulator of bone regeneration through dual mechanisms: restraining neutrophil hyperactivation via NF-κB/NLRP3 inhibition while cooperating with dsDNA to calibrate macrophage cGAS-STING signaling, revealing a targetable immunomodulatory axis for enhancing osseointegration. These findings provide new insights into the immune-bone regeneration interface and suggest novel therapeutic strategies for implant-related bone repair.
研究领域:
免疫学
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骨再生医学
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生物材料科学
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分子生物学
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炎症研究
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-14
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IF 10.435
Li Jiali,Li Shichao,Li Yang,Yuan Guanjie,Shen Yaqi,Peng Yang,Kong Li,Yang Conglian,Zhang Zhiping,Li Zhen
Background Immunochemotherapy is a potent anti-tumor strategy, however, how to select therapeutic drugs to enhance the combined therapeutic effect still needs to be explored. Methods and results Herein, a magnetic resonance nanoprobe (MnP@Lip) with STING (Stimulator of INterferon Genes) activation character was synthesized and co-administered with platinum-based chemotherapeutics for enhanced immunochemotherapy. MnP@Lip nanoparticles was prepared by simple fabrication process with good reproducibility, pH-sensitive drug release behavior and biocompatibility. In vitro experiments elucidated that Mn 2+ can promote the polarization of M0 and/or M2 macrophages to M1 phenotype, and promote the maturation of BMDC cells. Upon Mn 2+ treatment, the STING pathway was activated in tumor cells, mouse lung epithelial cells, and immune cells. More importantly, anti-tumor experiments in vivo proved that MnP@Lip combined with platinum-based chemotherapeutics increased T cells infiltration in the tumor microenvironment, and inhibited tumor growth in the orthotopic therapeutic and postoperative tumor models. Conclusions This kind of therapeutic strategy that combined MnP@Lip nanoparticles with platinum-based chemotherapeutics may provide a novel insight for immunochemotherapy. Graphical Abstract
研究领域:
癌症研究
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纳米技术
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免疫学
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药学
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Yahui Wu,Zhipu Liu,Yi Zhang,Senfeng Zhao,Miaoqing Li,Ruiyang Zhang,Jiahui Cao,Peng Liu,Liming Song,Yin Liu,Yunpeng Zhai,Weijie Wang,Ruopeng Liang,Rongtao Zhu,Yupeng Shi,Yuling Sun
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Photoimmunotherapy, which integrates photodynamic/photothermal therapy with immunomodulation, has emerged as a promising therapeutic strategy. However, its efficacy is often constrained by the immunosuppressive tumor microenvironment (TME) characteristic. Activation of the cGAS/STING signaling pathway represents a key mechanism for initiating innate immunity, thereby providing an attractive target for enhancing immunotherapy. In this study, we identified acetaminophen (APAP) as a potent in situ STING pathway activator capable of activating the cGAS/STING pathway and inducing apoptosis in HCC cells. To enable tumor-targeted delivery of APAP, we constructed a degradable nanoplatform termed GSST/APAP@HA. This system was fabricated by incorporating disulfide bonds into a Gd-TCPP-based amorphous metal-organic framework (MOF)-like networks (Gd-aMOF), loading it with APAP, and modifying the surface with hyaluronic acid (HA) for active targeting. Both in vitro and in vivo evaluations demonstrated efficient tumor accumulation of the nanoplatform and photodynamic-triggered immunogenic cell death (ICD), which provoked a robust antitumor immune response. Simultaneously, laser-induced reactive oxygen species (ROS) within the acidic TME promoted Gd-aMOF degradation and APAP release, leading to cGAS/STING pathway activation and remodeling of the immunosuppressive microenvironment. This combinatory approach resulted in significant tumor suppression in mouse HCC models. Coupled with its low cytotoxicity, excellent biocompatibility and superior magnetic resonance imaging (MRI) capability, the GSST/APAP@HA nanoplatform represents a promising theranostic strategy for cancer photoimmunotherapy.
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Nanomedicine
·
2026
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IF 3.9
Weixia Li,Yang Sun,Yi Guan,Xiao Zhi
Background Aluminum adjuvants remain the most widely used adjuvants in licensed vaccines. Their broader application, however, is restricted by local and systemic adverse effects and limited antigen compatibility, slowing vaccine development.Methods A nanoscale aluminum – fumarate metal – organic framework (AlFu‑MOF) was synthesized in water using Pluronic F127 and acetic acid. Based on this framework, a composite nanoadjuvant—(D)-mannose‑cTAT‑CpG@M@AlFu‑MOF (DCC@M@AlFu‑MOF) – was designed and characterized. The loading capacity for immunostimulatory cargos, including MSA‑2, CpG, cTAT, (D)-mannose, and OVA, was evaluated. Cellular uptake and immune activation of antigen‑presenting cells were tested in vitro. AlFu‑MOF displayed high loading efficiency and improved antigen availability. DCC@M@AlFu‑MOF promoted dendritic cell maturation and activation and also triggered the STING signaling pathway.Conclusion DCC@M@AlFu‑MOF is an aluminum‑based nanoadjuvant with potential dendritic cell‑targeting ability. It can coordinate innate immune signaling and shows promise for enhancing vaccine‑induced immune responses.
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ADVANCED MATERIALS
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2026
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IF 29.1
Han Chen,Haijing Qu,Yuqing Pan,Wei Cheng,Jie Wu,Ning Wang,Jiaqi Shen,Wei Meng,Zejian Wang,Xiangdong Xue
Endogenous STING activation by mitochondrial DNA (mtDNA) offers a tumor-context-dependent strategy with potentially reduced off-target toxicity, but is often limited by weak and transient mtDNA-driven STING signaling that fails to sustain robust STING clustering. Here, we developed an on-demand nanoparticle system that harnesses mitochondrial–ER functional interplay by concurrently inducing mtDNA release and ER stress, thereby relieving the STIM1-mediated brake on STING and enabling robust STING–TBK1 assembly and downstream signaling. This strategy markedly increased the phosphorylation levels of STING, TBK1, and IRF3 by 11.50-, 9.70-, and 8.95-fold, respectively, compared with PBS, outperforming the commercial STING agonist MSA-2 by more than 2-fold. In addition, the nanoparticles enabled spatially controlled co-delivery, allowing extracellular release of a PD-1/PD-L1 inhibitor and intracellular release of mtDNA-releasing and ER stress-inducing agents. Consequently, this on-demand nanoparticle system potently enhanced both innate and adaptive antitumor immunity in vivo, significantly increasing CD8 + and CD4 + T cell infiltration while reducing Tregs, ultimately suppressing tumor progression, metastasis, and recurrence in mouse models of breast and colon cancer. This strategy advances STING-based immunotherapy by integrating spatially staged drug release with organelle-level immune modulation.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Liu Wen,Jia Bin,Yang Feiya,Yin Lu,Tian Ziru,Sheng Guoli,Wang Wenkuan,Gao Yunhao,Zhang Lingpu,Wei Wenqiang,Xiao Haihua,Xing Nianzeng
Intravesical therapy is widely used in the management of bladder cancer. Nevertheless, continuous urinary flow accelerates the elimination of intravesically administered drugs, thereby reducing bladder residence time and therapeutic efficacy. Agents targeting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway have shown promising antitumor activity, yet their clinical translation is hindered by low local bioavailability and insufficient tumor selectivity. Here, a glutathione (GSH)-responsive nanoplatform, NP MP @Pt-MSA, was developed to integrate mucoadhesion with charge-mediated tissue penetration, thereby prolonging bladder retention and enhancing transurothelial delivery during intravesical administration. Upon cellular internalization, NP MP @Pt-MSA releases a Pt(IV) prodrug and the STING agonist MSA. DNA damage induced by the Pt(IV) prodrug promotes cytosolic dsDNA accumulation and activates the cGAS-STING pathway, while MSA further amplifies STING signaling, resulting in enhanced chemo-immunotherapeutic effects. In vivo, intravesical administration of NP MP @Pt-MSA significantly inhibited tumor growth, enhanced antitumor immune responses, and remodeled the immunosuppressive tumor microenvironment. Collectively, these findings establish a multifunctional intravesical delivery strategy that integrates mucoadhesive and tissue-penetrating nanoparticle design with dual chemo-immunomodulation, offering a promising approach to improve local therapy for bladder cancer. Graphical abstract
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Frontiers in Pharmacology
·
2026
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IF 5.4
Yize Zhang,Yifei Li,Yingqiao Qin,Shaomei Liang,Kunpeng Liu,Xue Liang
Introduction RNA virus infections often cause liver steatosis and lipid deposition, which significantly exacerbate liver damage. However, the underlying mechanisms linking viral-induced lipid accumulation to hepatocellular death remain incompletely understood. Methods We employed a primary mouse hepatocyte model of vesicular stomatitis virus (VSV) infection and an in vivo mouse model of virus-induced acute liver failure. The role of STING was investigated through genetic knockdown and pharmacological inhibition using H-151. Furthermore, clinical relevance was assessed using data from the National Health and Nutrition Examination Survey (NHANES, 2007–2010) to analyze correlations between hepatic steatosis and injury biomarkers. Results Viral exposure induced time-dependent upregulation and activation of STING, which driven the pathological accumulation of lipid droplets and subsequent ferroptotic cell death. Genetic knockdown or pharmacological inhibition of STING (H-151) effectively mitigated metabolic stress and preserved cell viability. These protective effects were recapitulated in vivo, where H-151 administration significantly improved survival and reduced tissue damage in a mouse model of virus-induced acute liver failure. Analysis of NHANES data corroborated these findings, showing that in patients with concurrent viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD), the fatty liver index (FLI) and triglyceride levels correlate linearly with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Conclusion Collectively, our study identifies the STING-lipotoxicity axis as a key driver of viral hepatotoxicity, highlighting its potential as a therapeutic target for liver injury.
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