ACS Nano
·
2024
·
IF 15.8
Yuhua Cao,Shuaishuai Ding,Yunping Hu,Lijuan Zeng,Jingrong Zhou,Ling Lin,Xiao Zhang,Qinghua Ma,Ruili Cai,Yu Zhang,Guangjie Duan,Xiu-wu Bian,Gan Tian
cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core–shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.
研究领域:
癌症生物学
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纳米技术
·
免疫学
·
放射肿瘤学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Jian Cai,Li Gao,Yue Wang,Yuanteng Zheng,Xiuling Lin,Pingzheng Zhou,Chunmei Chen,Kechun Liu,Lan Tang,Yonghong Liu,Yanhui Tan,Meng Jin,Xuefeng Zhou
Thirteen new sirenin derivatives named eupenicisirenins C–O ( 1 – 13 ), along with a biosynthetically related known one ( 14 ), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41410. The structures, which possessed a rare cyclopropane moiety, were confirmed by extensive analyses of the spectroscopic data , quantum chemical calculations , and X-ray diffraction. Among them, eupenicisirenin C ( 1 ) exhibited the strongest NF- κ B inhibitory activities, as well as suppressing effects on cGAS-STING pathway. Moreover, 1 showed the significant inhibitory effect on RANKL-induced osteoclast differentiation in bone marrow macrophages cells, and also displayed the therapeutic potential on prednisolone-induced zebrafish osteoporosis. Transcriptome analysis and the following verification tests suggested that its anti-osteoporotic mechanism is related to the extracellular matrix receptor interaction-related pathways. This study provided a promising marine-derived anti-osteoporotic agent for the treatment of skeletal disease.
研究领域:
海洋生物学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 11
·5817-5825
·
IF 7.79
Xiaohui Zhu,Wen Han,Yongfei Liu,Haihui Wang,Danying Lin,Zhangcheng Fu,Yu He,Xiaofei Yin,Chunhua Lu,Huanghao Yang
Photothermal therapy (PTT) has been extensively used as an effective therapeutic approach against cancer. However, PTT can trigger the proinflammatory response of dendritic cells (DCs) and macrophages to release proinflammatory cytokines, which can simulate tumor regeneration and further hinder subsequent therapy. Hence, an effective therapeutic system, comprising gold nanoparticle modified Cu2ZnSnS4 nanocrystals and aspirin (Au-CZTS/Asp), was developed to co-deliver PTT agents and inflammatory inhibitors for the synergistic treatment of cancer. Au-CZTS with high near infrared (NIR) photothermal conversion abilities can effectively induce apoptosis and tumor ablation under NIR light. Furthermore, Asp can inhibit the activation of the cGAS-STING pathway in DCs and the polarization of macrophages to intercept the PTT mediated inflammatory responses. Therefore, the as-prepared Au-CZTS/Asp can effectively realize the integration of tumor treatment and recovery. Simultaneously, the Au-CZTS/Asp with ultrasmall size can be rapidly cleared to reduce biotoxicity and side effects. In addition, the Au-CZTS/Asp showed excellent photoacoustic (PA) imaging properties around the tumor in vivo. Thus, our study provides a potential platform for a nano-prodrug that is viable for cancer diagnostic-treatment-recovery integration.
研究领域:
癌症治疗
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纳米技术
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药学
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免疫学
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产品关联
DOI
PubMed
高影响因子
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
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组织工程
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力学生物学
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细胞衰老
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退行性疾病
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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
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癌症免疫疗法
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纳米技术
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分子生物学
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细胞生物学
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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
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产品关联
DOI
PubMed
高影响因子
NUCLEIC ACIDS RESEARCH
·
2021
·Vol. 49
·期 21
·12306-12319
·
IF 16.971
Wang Huawei,Shan Xiajing,Ren Mengtian,Shang Mengdi,Zhou Chuanzheng
DNA damage and apoptosis lead to the release of free nucleosomes—the basic structural repeating units of chromatin—into the blood circulation system. We recently reported that free nucleosomes that enter the cytoplasm of mammalian cells trigger immune responses by activating cGMP-AMP synthase (cGAS). In the present study, we designed experiments to reveal the mechanism of nucleosome uptake by human cells. We showed that nucleosomes are first absorbed on the cell membrane through nonspecific electrostatic interactions between positively charged histone N-terminal tails and ligands on the cell surface, followed by internalization via clathrin- or caveolae-dependent endocytosis. After cellular internalization, endosomal escape occurs rapidly, and nucleosomes are released into the cytosol, maintaining structural integrity for an extended period. The efficient endocytosis of extracellular nucleosomes suggests that circulating nucleosomes may lead to cellular disorders as well as immunostimulation, and thus, the biological effects exerted by endocytic nucleosomes should be addressed in the future.
研究领域:
细胞生物学
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免疫学
·
分子生物学
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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
·
生物无机化学
·
肿瘤微环境
·
前药设计
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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
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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
危险品化学品经营许可证（带存储）