JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·
IF 12.6
Xinyao Hu,Hua Zhu,Yang Shen,Lang Rao,Jiayi Li,Xiaoqin He,Ximing Xu
Tumor immunotherapy aims to harness the immune system to identify and eliminate cancer cells. However, its full potential is hindered by the immunosuppressive nature of tumors. Radiotherapy remains a key treatment modality for local tumor control and immunomodulation within the tumor microenvironment. Yet, the efficacy of radiotherapy is often limited by tumor radiosensitivity, and traditional radiosensitizers have shown limited effectiveness in hepatocellular carcinoma (HCC). To address these challenges, we developed a novel multifunctional nanoparticle system, ZIF-8@MnCO@DOX (ZMD), designed to enhance drug delivery to tumor tissues. In the tumor microenvironment, Zn²⁺ and Mn²⁺ ions released from ZMD participate in a Fenton-like reaction, generating reactive oxygen species (ROS) that promote tumor cell death and improve radiosensitivity. Additionally, the release of doxorubicin (DOX)-an anthracycline chemotherapeutic agent-induces DNA damage and apoptosis in cancer cells. The combined action of metal ions and double-stranded DNA (dsDNA) from damaged tumor cells synergistically activates the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, thereby initiating a robust anti-tumor immune response. Both in vitro and in vivo experiments demonstrated that ZMD effectively activates the cGAS-STING pathway, promotes anti-tumor immune responses, and exerts a potent tumor-killing effect in combination with radiotherapy, leading to regression of both primary tumors and distant metastases. Our work provides a straightforward, safe, and effective strategy for combining immunotherapy with radiotherapy to treat advanced cancer.
研究领域:
肿瘤学
·
免疫学
·
放射生物学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aggregate
·
2025
·
IF 13.7
Xiaojiang Zhang,Yujie Zhang,Pengqian Wang,Feiyu Shi,Siyuan Du,Zhe Zhang,Daocheng Wu,Junjun She,Ya Wang
To improve the long-term therapeutic efficacy of colorectal cancer, we propose a synergistic treatment strategy involving dual-pathway, multistep induction of long-term hyperimmunity combined with photothermal-chemotherapy. To implement this strategy, infinite coordination polymer nanoparticles (SN38-Mn(II)-EGCG ICP NPs) were prepared by coordinating SN38, EGCG, and Mn 2+ . These nanoparticles were then coated with polydopamine (PDA) and grafted with folate-PEG-thiol (FA-PEG-SH) onto their surfaces, producing tumor-targeting folate-modified PDA infinite coordination polymer nanocomposites (ICP@FA-PDA nanocomposites). These nanocomposites exhibit a particle size of 94.9 ± 1.6 nm with a high drug loading capacity (83.3% ± 1.5%), drug release under acidic conditions while maintaining stability in physiological environments. Furthermore, each component within the nanocomposites serves multiple functions. Notably, the incorporation of multiple components triggers a powerful antitumor immune effect and establishes enduring immune memory through a dual-pathway and multistep approach, which is produced with the activation of the cGAS-STING pathway and immunogenic cell death (ICD) by a four-component multistep process. Under a low-dose regimen, this approach induces dual-pathway hyperimmunity effect and generates ultra-long immunological memory, marked by a ninefold increase in CD8 + T cell infiltration, a fourfold increase in CD4 + T lymphocytes, a fourfold reduction in Treg cells, and a fivefold increase in memory T cells. The remarkable therapy efficacy is achieved by hyperimmunity effect combination of SN38 and EGCG chemotherapy and photothermal therapy. In vivo studies demonstrated that mice treated with ICP@FA-PDA nanocomposites achieved complete eradication of cancer within 21 days, with no recurrence observed within 60 days. These nanocomposites hold significant promise and potential for future clinical translation.
研究领域:
癌症治疗
·
纳米医学
·
免疫学
·
化学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Zhiyan Li,Xianghui Li,Yanjun Lu,Xudong Zhu,Wenxuan Zheng,Kai Chen,Xingzhou Wang,Tao Wang,Wenxian Guan,Zhi Su,Song Liu,Jinhui Wu
Immunotherapy has emerged as a highly effective therapeutic strategy for cancer treatment. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway activation facilitates tumor-associated macrophage (TAM) polarization toward M1 phenotype, and Mn 2+ are effective agents for this pathway activation. However, the high in vivo degradation rate and toxicity of Mn 2+ hamper clinical application of immunotherapy. Here, this work has newly synthesized and screened manganese porphyrins for Mn 2+ transport, referred to as photo-STING agonists (PSAs), and further encapsulate them into core-shell nanoparticles named Rm@PP-GA with dual specificity for tumor tissue and TAMs. Not only do PSAs achieve higher Mn 2+ delivery efficiency compared to Mn 2+ , but they also generate reactive oxygen species under light exposure, promoting mitochondrial DNA release for cGAS-STING pathway activation. In Rm@PP-GA, globin and red blood cell membranes (Rm) are used for erythrocyte efferocytosis-mimicking delivery. Rm can effectively prolong the in vivo circulation period while globin enables PSAs to be taken up by TAMs via CD163 receptors. After Rm rupture mediated by perfluorohexane in nanoparticles under ultrasonication, drugs are specifically released for TAM repolarization. Further, dendritic cells mature, as well as T lymphocyte infiltrate, both of which favor tumor eradication. Therefore, cancer immunotherapy is optimized by novel PSAs delivered by erythrocyte efferocytosis-mimicking delivery pattern.
研究领域:
肿瘤学
·
免疫疗法
·
药学
·
纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Xin-Yu Xiao,Qian-Wei Luo,Wang-Shu Li,Ze-Kun Chen,Zhuo Yang,Ya-Xuan Zhu,Mu-Rong Lei,Fang-Fang Zhuo,Ming Yu,Tian-Tian Wei,Hong-Wei Jin,Zhong-Yao Li,Zhi-Yuan Lu,Zhu-Qing Zhang,Hua Wang,Yong-Cheng Wang,Qing Xia,Wei Yu,Bo Han,Peng-Fei Tu,Ke-Wu Zeng
Nanoparticles bind to proteins in cells selectively and form a protein corona around them. However, the mechanisms of protein conformational changes underlying the interactions between nanoparticles and protein coronas remain poorly understood. In this study, we prepared small molecule self-assembled nanoparticles (Aloin NPs) as a research tool to investigate the allosteric mechanism of protein coronas. Aloin NPs showed a propensity to capture multiple proteins in cells. In particular, Aloin NPs specifically bound to myotrophin (MPTN) as a major protein corona through a multivalent hydrogen bond-mediated nanoprotein interface. Molecular modeling and hydrogen–deuterium exchange mass spectrometry (MS) demonstrated that Aloin NPs promoted a conformational rearrangement of MPTN via a ‘finger-unclasping’ pattern. We then adapted the APEX2 proximity labeling strategy to investigate the conformation-dependent changes in the MPTN interactome and identified peroxiredoxin 6 (PRDX6) as a key substrate protein of MPTN in microglia. Additionally, we observed that MPTN conformational change-dependent PRDX6 release protected the mitochondrial membrane by reducing reactive oxygen species. Consequently, Aloin NPs effectively inhibited the release of mitochondrial DNA to block the downstream cGAS-STING signaling pathway, thereby reprogramming microglial polarization. In translational medicine, Aloin NPs play a role in protecting neurons from microglia-induced inflammatory injury with no significant adverse effects, ultimately improving Parkinson’s disease-associated symptoms. Taken together, our study provides insights into the molecular mechanisms by which nanoparticles regulate the conformational change of protein coronas for human disease therapy.
研究领域:
纳米技术
·
生物化学
·
细胞生物学
·
神经科学
·
免疫学
·
结构生物学
·
药理学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Huang Zhusheng,Huang Shiqian,Song Simin,Ding Yankui,Zhou Hao,Zhang Shaoyin,Weng Lixing,Zhang Ying,Hu Yiqiao,Yuan Ahu,Dai Yunlu,Luo Zhimin,Wang Lianhui
The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T 2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫治疗
·
放射治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Cuixia Zheng,Qingling Song,Hongjuan Zhao,Yueyue Kong,Lingling Sun,Xinxin Liu,Qianhua Feng,Lei Wang
The failure of any phase in continuous multi-link immune response process can cause unsatisfactory outcomes, which might be improved by all-cancer-immunity-cycle boosted strategy. Herein, a nanoplatform Mn/CaCO 3 @PL/SLC is developed, which is based on palmitoyl ascorbate (PA)-liposome (PL) loaded with Mn-doped CaCO 3 nanoparticles (Mn/CaCO 3 NPs) and carbonic anhydrase (CAIX) inhibitor SLC-0111. The nanoplatform comprehensively amplifies all immune stages including tumor-associated antigens (TAAs) release and presentation, T cells activation and infiltration , as well as tumor cells destruction. In detail, Mn-triggered lipid peroxidation facilitates TAAs release and subsequent T cells activation to initiate immunity cycle. Additionally, SLC-0111 and PA amplify the infiltration and tumor killing activity of these effector T cells. The former polarizes the immunosuppressive tumor microenvironment to an immune-active phenotype and the latter enhances the function of tumor-infiltrating T lymphocytes. Importantly, Mn augments the all-immunity-cycle by promoting cGAS-STING pathway activation. In summary, the Mn/CaCO 3 @PL/SLC nanoplatform is verified to boost anti-tumor immunity and achieve outstanding immunotherapeutic effects in eradicating tumor and preventing tumor metastasis. Such an all-cancer-immunity-cycle boosted strategy is meaningful for antitumor immunotherapy .
研究领域:
纳米技术
·
免疫学
·
肿瘤学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2023
·
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.
研究领域:
纳米技术
·
免疫学
·
药学
·
分子生物学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2023
·
IF 15.1
Lin Ding,Minli Liang,Yuanyuan Li,Mei Zeng,Meiting Liu,Wei Ma,Fuming Chen,Chenchen Li,Rui L. Reis,Fu-Rong Li,Yanli Wang
Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason for immunotherapy failure. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway plays a key role in activating CD8 + T cells, maintaining CD8 + T cells stemness and enhancing the antitumor effect. Herein, a zinc-organometallic framework vaccine (ZPM@OVA-CpG) prepared by self-assembly, which achieves site-directed release of Zn 2+ in dendritic cell (DC) lysosomes and tumor microenvironment under acidic conditions, is reported. The vaccine actively targets DC, significantly enhances cGAS-STING signal, promotes DC maturation and antigen cross-presentation, and induces strong activation of CD8 + T cells. Meanwhile, the vaccine reaches the tumor site, releasing Zn 2+ , significantly up-regulates the activity of matrix metalloproteinase-2, degrades various collagen components of tumor ECM, effectively alleviates immune suppression, and significantly enhances the tumor infiltration and killing of CD8 + T cells. ZPM@OVA-CpG vaccine not only solves the problem of low antigen delivery efficiency and weak CD8 + T cells activation ability, but also achieves the degradation of tumor ECM via the vaccine for the first time, providing a promising therapeutic platform for the development of efficient novel tumor vaccines.
研究领域:
癌症免疫学
·
药学
·
生物医学工程
·
分子生物学
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Shilin Zhou,Yuxuan Sun,Kaidi Wang,Xintao Gao,Kehong Dong,Jing Wang,Xiaochen Wu,Chuanlong Guo
Oxaliplatin (OXL) is a first-line drug for the treatment of colon cancer , with excellent efficacy. Intestinal toxicity is a common side effect of OXL, with unclear pathogenesis and a lack of effective treatment strategies. Polydatin (PD) has anti-inflammatory and antioxidant activities and is a potential drug for treating intestinal diseases , but its poor water solubility limits its application. In this study, polyvinylpyrrolidone (PVP) was used as a carrier to prepare nanoparticles loaded with PD (PVP-PD), with a particle size of 92.42 nm and exhibiting sustained release properties. In vitro results showed that PVP-PD protected NCM460 cells from OXL induced injury, mitochondrial membrane potential (MMP) disruption, and accumulation of reactive oxygen species (ROS). The in vivo results demonstrated the protective effect of PVP-PD on intestinal toxicity induced by OXL, such as alleviating weight loss and colon length reduction induced by OXL. Both in vivo and in vitro mechanisms indicated that OXL induced DNA damage and activated the cGAS-STING pathway, further inducing the expression of inflammatory factors such as IL-1β and TNF-α. PVP-PD alleviated the aforementioned changes induced by OXL by inhibiting the DNA damage-cGAS-STING pathway. In summary, our study demonstrated that the DNA damage-cGAS-STING pathway was involved in OXL induced intestinal toxicity, and PVP-PD provided a potential strategy for treating OXL induced intestinal toxicity.
研究领域:
药理学
·
毒理学
·
纳米技术
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Weitao Wang,Haitao Wu,Xuan Zhang,Yang Hong,Shi Tao,Xiangjing Cao,Shipeng Wang,Lisha Zha,Zhengbao Zha
Using entire tumor cells or tissues that display both common and patient-specific antigens can potentially trigger a comprehensive and long-lasting anti-tumor immune response. However, the limited immunogenicity, low uptake efficiency, and susceptibility to degradation of whole-component antigens present significant challenges. In this study, we employed tumor lysates (TLs) as whole-component antigens, in conjunction with MgAl-layered double hydroxide (MA) as nanoadjuvants and Mn 2+ as immunostimulants, to create personalized MMAT (Mn 2+ -MA-TLs) nanovaccines. After subcutaneous injection of MMAT nanovaccines, the high local concentrations of TLs and Mn 2+ facilitated the recruitment and activation of antigen-presenting cells (APCs), thereby inducing a robust adaptive immune response. Remarkably, MMAT nanovaccines enabled lysosomal escape, enhanced antigen cross-presentation, and activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in APCs. Furthermore, MMAT nanovaccines, when combined with the anti-TIGIT monoclonal antibody (aTIGIT), an immune checkpoint inhibitor, not only stimulated T-cell-based adaptive anti-tumor immune responses but also activated the NK-cell-based innate anti-tumor immunity, effectively suppressing tumor growth, recurrence, and metastasis. Thus, the ternary MMAT nanovaccines developed here introduced a pioneered paradigm for the rapid preparation of whole-component tumor antigens with nanoadjuvants and immunostimulants into nanovaccines, offering new prospects for clinical immunotherapies.
研究领域:
癌症免疫疗法
·
免疫学
·
纳米医学
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2022
·
IF 4.631
Renhui Huang,Qi Shi,Shutian Zhang,Hong Lin,Chengzhi Han,Xinyi Qian,Yijun Huang,Xiaorong Ren,Jiayuan Sun,Nana Feng,Chunmei Xia,Meng Shi
Purpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS.Methods: We used Sprague-Dawley rats to make the lung I/R model by performing left hilum occlusion-reperfusion surgery. cGAS-specific inhibitor RU.521, STING agonist SR-717, and 4-phenylbutyric acid (4-PBA), the ERS inhibitor, were intraperitoneally administered in rats. Double immunofluorescent staining was applied to detect the colocalization of cGAS or BiP, an ERS protein, with alveolar epithelial type II cells (AECIIs) marker. We used transmission electron microscopy to examine the ultrastructure of ER and mitochondria. Apoptosis and oxidative stress in the lungs were assessed, respectively. The profiles of pulmonary edema and lung tissue injury were evaluated. And the pulmonary ventilation function was measured using a spirometer system.Results: In lung I/R rats, the cGAS-STING pathway was upregulated, which implied they were activated. After cGAS-STING pathway was inhibited or activated in lung I/R rats, the ERS was alleviated after cGAS was inhibited, while when STING was activated after lung I/R, ERS was aggravated in the AECIIs, these results suggested that cGAS-STING pathway might trigger ERS responses. Furthermore, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats. Inhibition of cGAS-STING pathway attenuated ERS, therefore attenuated lung injury and promoted pulmonary ventilation function in I/R rats.Conclusion: Inhibition of the cGAS-STING pathway attenuates lung ischemia/reperfusion injury via alleviating endoplasmic reticulum stress in alveolar epithelial type II cells of rats.
研究领域:
免疫学
·
病理生理学
·
呼吸医学
·
分子生物学
✓ 已验证
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
·
药理学
·
生物化学
·
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）