ACS Nano
·
2025
·
IF 16
Ziang Li,Jincheng Tang,Liang Zhou,Jiannan Mao,Wei Wang,Ziyan Huang,Lichen Zhang,Jie Wu,Xinzhao Jiang,Zhouye Ding,Kun Xi,Feng Cai,Yong Gu,Liang Chen
The extracellular matrix (ECM) stores signaling molecules and facilitates mechanical and biochemical signaling in cells. However, the influence of biomimetic “rejuvenation” ECM structures on aging- and degeneration-related cellular activities and tissue repair is not well understood. We combined physical extrusion and precise “on–off” alternating cross-linking methods to create anisotropic biomaterial microgels (MicroRod and MicroSphere) and explored how they regulate the cell activities of the nucleus pulposus (NP) and their potential antidegenerative effects on intervertebral discs. NP cells exhibited aligned growth along the surface of the MicroRod, enhanced proliferation, and reduced apoptosis. This suggests an adaptive cellular response involving adhesion and mechanosensing, which causes cytoskeletal extension via environmental cues. NP cells maintain nuclear membrane integrity through the YAP/TAZ pathway, which activates the cGAS-STING pathway to rectify the aging mechanisms. In vivo, MicroRod carries NP cells and reduces inflammatory factor and protease secretion in degenerated intervertebral discs, inhibiting degeneration and promoting NP tissue regeneration. Our findings highlight the role of mechanical stress in maintaining cellular activity and antiaging effects in harsh environments, providing a foundation for further research and development of antidegenerative biomaterials.
研究领域:
生物材料
·
组织工程
·
力学生物学
·
细胞衰老
·
退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 37
·2204585
·
IF 32.086
Xiu Zhao,Yiyang Wang,Wenxiao Jiang,Qiongwei Wang,Jun Li,Zhiyang Wen,Airong Li,Kaixiang Zhang,Zhenzhong Zhang,Jinjin Shi,Junjie Liu
Virus-based immunotherapy is a promising approach to treat tumor. Closely mimicking the structure and sequential infection processes of natural viruses is highly desirable for effective tumor immunotherapy but remains challenging. Here, inspired by the robust innate immunity induced by herpesvirus, a herpesvirus-mimicking nanoparticle (named Vir-ZM@TD) is engineered for tumor therapy by mimicking the structure and infection processes of herpesvirus. In this biomimetic system, DNAzyme-loaded manganese‑doped zeolitic imidazolate framework‑90 (ZIF-90) nanoparticles (ZM@TD) mimic the virus nucleocapsid containing the genome; the erythrocyte membrane mimics the viral envelope; and two functional peptides, RGD and HA2 peptides, resemble the surface glycoprotein spikes of herpesvirus. Vir-ZM@TD can both effectively evade rapid clearance in the blood circulation and closely mimic the serial infection processes of herpesvirus, including specific tumor targeting, membrane fusion-mediated endosomal escape, and TFAM (transcription factor A, mitochondrial) deficiency-triggered mitochondrial DNA stress, as well as the release of manganese ions (Mn 2+ ) from organelles into the cytosol, ultimately effectively priming cGAS-STING pathway-mediated innate immunity with 68% complete regression of primary tumors and extending by 32 days the median survival time of 4T1-tumor-bearing mice.
研究领域:
生物医学工程
·
癌症免疫疗法
·
纳米技术
·
分子生物学
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细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Shiyu Zhang,Siyi Li,Xiucheng Zhao,Wubin Lv,Yuxuan Zhao,Lei Zhong,Shili Gai,He Ding,Ruizheng Liang,Piaoping Yang
Ion-overload-mediated pyroptosis can enhance cytotoxic T-cell infiltration and systemic immunity, presenting a promising strategy to strengthen immunotherapy efficacy. However, the low frequency of pro-inflammatory immune cells and the immunosuppressive tumor network pose substantial challenges to achieving potent immunogenic cell death. This study designs a multiphase phase-transition nano-disruptor (V-MoS 2 &CaF 2 @HA), inspired by ionic interference and metabolic inhibition, to target multiple immunosuppressive mechanisms in tumors. Vanadium-doping engineering induces the coexistence of the 2H (semiconducting) and 1T (metallic) phases, maximizing the ability of piezocatalysts to enhance charge-carrier mobility. Critically, V-MoS 2 with its ultrathin, asymmetrical layered architecture, reinforces the piezoelectric response by promoting band bending and charge-carrier separation, thereby establishing favorable conditions for efficient electron–hole separation and reactive oxygen species generation. Concurrently, calcium-ion self-amplifying leakage and hydrogen sulfide liberation collectively create an “ion-interference–metabolic-hijacking” effect that induces oxidative stress, amplifies innate immune cGAS–STING pathway activation, and triggers a pyroptosis–apoptosis cross-death effect and immune activation. Thus, the study offers a straightforward strategy to achieve antitumor immunity through STING pathway activation and provides a new avenue to robustly activate immunogenic cell death for tumor treatment.
研究领域:
纳米医学
·
癌症免疫治疗
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生物医学工程
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活性氧信号传导
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肿瘤微环境
·
免疫原性细胞死亡
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yingpei Yao,Zijie Lu,Chao Fang,Shuyue Chang,Yongjun Wu,Xiang Li,Junwei Zhao,Yike Fu,Xiang Li
Chemotherapy remains a mainstream cancer therapy but is hindered by severe side effects and limited durable cancer control. Smart nanomedicines that integrate prodrug delivery and immune modulation may offer potential opportunities to tackle the daunting challenges. Herein, an acid-responsive nanocarrier (ZZTA) consisting of ZnO 2 , ZIF-8, and Zn-tannic acid is developed. A phenylboronic ester prodrug (BDOX) is synthesized and integrated with ZZTA, creating a multifunctional nano-prodrug, ZZTA-BDOX. The yolk-shell structure of ZZTA prevents premature decomposition of ZnO 2 during circulation, and enables sustained release of Zn 2+ and H 2 O 2 in response to the acidic tumor microenvironment. The generated H 2 O 2 subsequently activates BDOX, releasing cytotoxic DOX intracellularly. Meanwhile, the Zn 2+ released enhances cGAS-STING signaling, promoting dendritic cell maturation and T cell priming, which results in clear systemic antitumor immune responses. The in vivo study demonstrates that ZZTA-BDOX nano-prodrug not only enables efficient tumor inhibition but also suppresses metastasis through immune activation.
研究领域:
纳米医学
·
癌症免疫治疗
·
药物递送系统
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生物无机化学
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肿瘤微环境
·
前药设计
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Chengyao Huang,Ke Zhang,Yu Ren,Xihong Liu,Yan Li,Bangliu Yang,Peiran Chen,Mingyue Zhang,Xiaotong Lu,Yuhong Zhuo,Chao Qi,Kaiyong Cai
Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn 2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H 2 O 2 ), which not only alleviates the ISME, but also provides reactants for the Mn 2+ -mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn 2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. Statement of significance To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn 2+ ions in the acidic tumor microenvironment. The released LOX generates H 2 O 2 for the Mn 2+ -mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn 2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.
研究领域:
癌症研究
·
免疫治疗
·
纳米医学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Bulletin
·
2024
·
IF 18.8
Gang Wang,Jingrui Li,Shumin Sun,Yuqi Yang,Zhihui Han,Zifan Pei,Liang Cheng
Excess intracellular H 2 S induces destructive mitochondrial toxicity, while overload of Zn 2+ results in cell pyroptosis and potentiates the tumor immunogenicity for immunotherapy. However, the precise delivery of both therapeutics remains a great challenge. Herein, an electrically activable ZnS nanochip for the controlled release of H 2 S and Zn 2+ was developed for enhanced gas-ionic-immunotherapy (GIIT). Under an electric field, a locality with particularly high concentrations of H 2 S and Zn 2+ was established by the voltage-controlled degradation of the ZnS nanoparticles (NPs). Consequently, the ZnS nanochip-mediated gas-ionic therapy (GIT) resulted in mitochondrial membrane potential depolarization, energy generation inhibition, and oxidative stress imbalance in tumor cells. Interestingly, the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway was activated due to the mitochondrial destruction. Moreover, the released Zn 2+ resulted in the increase of the intracellular Zn levels and cell pyroptosis, which enhanced the immunogenicity via the release of damage-associated molecular patterns (DAMPs). In vitro and in vivo studies revealed that the ZnS nanochip-based GIT effectively eliminated the tumors under an electric field and mobilized the cytotoxic T lymphocytes for immunotherapy. The combination with αCTLA-4 further promoted the adaptive immune response and inhibited tumor metastasis and long-term tumor recurrence. This work presented an electrically activable ZnS nanochip for combined immunotherapy, which might inspire the development of electric stimulation therapy.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Pei Pei,Yu Zhang,Yunchun Jiang,Wenhao Shen,Hua Chen,Sai Yang,Yanxiang Zhang,Xuan Yi,Kai Yang
Biomaterial-based pleiotropic immune activation may effectively improve the response rate of immunotherapy and enhance the therapeutic effect of the tumor. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and immune activation of the body. Herein, we construct an inactivated bacteria vector with 125I/131I labeling (125I-VNP/131I-VNP), which could retain radioiodine at the tumor site for a long time and deliver it into tumor cells and a tumor-associated macrophage (TAM), thus achieving efficient internal radioisotope therapy (IRT) of the primary tumor with good biosafety. More importantly, 131I-VNP-mediated local IRT could further stimulate robust systemic antitumor immune responses via activation of the cGAS-STING pathway of innate immunity and promotion of the maturation of DC cells for T-cell-dominated adaptive immunity. After combination with systemic checkpoint blockade therapy (αPD-L1), 131I-VNP, which induces the up-regulation of PD-L1 expression in the distant tumor, could lead to the inhibition of in situ colon cancer and protection against tumor rechallenge. Our strategy pioneers the use of an inactivated bacteria vector as a bridge to cleverly connect radiotherapy and immunotherapy and provide an enlightening idea for radio-immunotherapy mediated by pleiotropic immune activation functions of bacterial vectors.
研究领域:
癌症免疫疗法
·
放射生物学
·
分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Science Bulletin
·
2025
·
IF 21.1
Fangke Zhang,Jiancheng Zheng,Fei Wang,Yaping Zhuang,Yunkai Tang,Juan Wang,Yawei Du,Wei-Li Zhao,Min Lu,Weiguo Hu,Wenguo Cui
Mutations in cytoplasmic DNA-degrading enzymes can lead to the accumulation of cytoplasmic DNA (cytoDNA), which excessively activates DNA-sensing pathways and exacerbates inflammatory aging. Reducing cytoDNA levels to suppress DNA-sensing mechanisms is therefore critical for treating elderly-onset rheumatoid arthritis (EORA). In this study, we constructed Trex1 mRNA loaded lipid nanoparticles (LNPs) via microfluidics and prepared DNase I loaded polydopamine (PDA) nanoparticles through oxidative polymerization. These two components were co-encapsulated into methacrylated hyaluronic acid (HAMA) microspheres using microfluidic photopolymerization. The LNPs incorporate cationic lipids to facilitate mRNA loading and promote endosomal escape, enabling efficient translation of TREX1 and subsequent recognition and degradation of cytoDNA. Meanwhile, cationic mesoporous polydopamine electrostatically adsorbs and degrades extracellular DNA. The microspheres function as a reservoir for sustained nanoparticle release, enabling synergistic inhibition of DNA sensing pathways. This microsphere based vaccine upregulates TREX1 expression in antigen-presenting cells (APCs) and reduces cytoDNA levels, thereby suppressing overactivation of the cGAS-STING signaling axis and promoting immune tolerance. It also attenuates the differentiation of CD4+ T cells into Th1, Th2, Th17, and Treg subsets. In an aged rat model of rheumatoid arthritis, the vaccine alleviated soft tissue swelling, synovitis, and cartilage and bone damage. By clearing excess cytoDNA and restraining DNA-sensing hyperactivation, this vaccine induces cellular immune tolerance and represents a promising therapeutic strategy for rheumatoid arthritis in the elderly.
研究领域:
免疫学
·
纳米医学
·
分子生物学
·
疫苗学
·
风湿病学
·
衰老研究
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Chen Yang,Tian Hailong,Zhang Xiaodian,Nice Edouard C.,Huang Canhua,Zhang Haiyuan,Zheng Shaojiang
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photodynamic therapy (PDT) mediated reactive oxygen species (ROS) accumulation and Cu 2+ triggered cuproptosis, resulting in evoking the AMP-activated protein kinase (AMPK) pathway to degrade PD-L1, and activating the cGAS-STING pathway to enhance anti-tumor immunity. Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy. Graphical
研究领域:
癌症研究
·
纳米技术
·
免疫学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2024
·
IF 8.1
Mingxiao Fang,Jun Zheng,Jingxue Wang,Chenpeng Zheng,Xiaojing Leng,E. Wen,Pan Li,Haitao Ran,Liang Zhang,Zhigang Wang
The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (•OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5′-monophosphate–adenosine 5′-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS–STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.
研究领域:
免疫疗法
·
癌症生物学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Su Zheng,Xu Dongdong,Hu Xianli,Zhu Wanbo,Kong Lingtong,Qian Zhengzheng,Mei Jiawei,Ma Ruixiang,Shang Xifu,Fan Wenpei,Zhu Chen
Pathogen-host competition for manganese and intricate immunostimulatory pathways severely attenuates the efficacy of antibacterial immunotherapy against biofilm infections associated with orthopaedic implants. Herein, we introduce a spatiotemporal sono-metalloimmunotherapy (SMIT) strategy aimed at efficient biofilm ablation by custom design of ingenious biomimetic metal-organic framework (PCN-224)-coated MnO 2 -hydrangea nanoparticles (MnPM) as a metalloantibiotic. Upon reaching the acidic H 2 O 2 -enriched biofilm microenvironment, MnPM can convert abundant H 2 O 2 into oxygen, which is conducive to significantly enhancing the efficacy of ultrasound (US)-triggered sonodynamic therapy (SDT), thereby exposing bacteria-associated antigens (BAAs). Moreover, MnPM disrupts bacterial homeostasis, further killing more bacteria. Then, the Mn ions released from the degraded MnO 2 can recharge immune cells to enhance the cGAS-STING signaling pathway sensing of BAAs, further boosting the immune response and suppressing biofilm growth via biofilm-specific T cell responses. Following US withdrawal, the sustained oxygenation promotes the survival and migration of fibroblasts, stimulates the expression of angiogenic growth factors and angiogenesis, and neutralizes excessive inflammation. Our findings highlight that MnPM may act as an immune costimulatory metalloantibiotic to regulate the cGAS-STING signaling pathway, presenting a promising alternative to antibiotics for orthopaedic biofilm infection treatment and pro-tissue repair.
研究领域:
生物医学工程
·
材料科学
·
免疫学
·
骨科
·
传染病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Heying Chen,Xiaomeng Cai,Jiayu Zhang,Hongyan Sun,Jie Zhang,Jun Chen,Zhenglin Yang,Dongqing Wang
Combination of chemotherapy and cancer immunotherapy has shown substantial clinical promise. However, the immunosuppressive tumor microenvironment (TME) poses a critical barrier to this combination therapy. Here, a tumor lysosome-targeted immunomodulatory strategy based on a biomimetic nanoadjuvant is presented, which effectively overcomes the immunosuppressive TME and demonstrates enhanced therapeutic efficacy when combined with chemotherapy. This nanoadjuvant integrates Fe-DOX coordination nanoparticles, a MnCO 3 shell, TLR7/8 agonist (R848), and a mature dendritic cell membrane (DCM) coating. The resulting DCM@(Fe-DOX-Mn-R848) nanoadjuvant induces immunogenic cell death in tumor cells via lysosomal-mitochondrial cascade destruction. Concurrently, it activates the cGAS-STING signaling pathway to promote dendritic cell maturation and repolarize tumor-associated macrophages from M2 to M1 phenotype, thereby effectively enhancing CD8 + T cell activation and tumor therapeutic efficacy. When combined with PD-L1 blockade therapy, the nanoadjuvant demonstrates enhanced efficacy in murine models of primary and recurrent triple-negative breast cancer, establishing durable immune memory. This platform demonstrates significant potential in overcoming immunosuppressive TME and advancing combination therapy through lysosome-targeting drug delivery technology, revealing promising prospects for cancer treatment.
研究领域:
纳米医学
·
免疫学
·
癌症生物学
·
生物工程
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）