Nano Today
·
2022
·
IF 18.962
Hao Tian,Guohao Wang,Wei Sang,Lisi Xie,Zhan Zhang,Wenxi Li,Jie Yan,Ye Tian,Jie Li,Bei Li,Yunlu Dai
Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy . Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn 2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn 2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced cancer immunotherapy.
研究领域:
癌症研究
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免疫学
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纳米技术
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治疗学
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Xiangkai Zhang,Yangzi Yang,Jiaxin Li,Xinru Xie,Yongqiang Hao,Yingchun Zhu,Zhiyuan Zhang,Jingke Fu,Hailong Ma
Immunotherapy is a revolutionary achievement in cancer treatment. However, inadequate immune cells infiltration in tumor microenvironment (TME) always leads to treatment failure. Moreover, hypoxic TME hampers normal functions of immune cells. Here, it is found that hypoxia suppresses the STING signaling and immune cells activation in the work. Remodeling tumor immune microenvironment and relieving hypoxia are thus essential for enhancing immunotherapy efficiency. Herein, a spirulina platensis (SP)-based magnetic biohybrid system is constructed as an oxygen factory and loaded with stimulator of interferon genes (STING) agonist ADU-S100 (ADU@Fe-SP) for tumor immunotherapy. Magnet-guided biohybrid SP can actively target tumor tissues and produce oxygen in situ through photosynthesis, which reverses the hypoxic TME and facilitates the function of immune cells. Besides, the targeted delivery of ADU-S100 can activate the STING/TBK1/IRF3 signaling and boost cytokines production in tumor and innate immune cells. The ADU@Fe-SP system thus induces efficient immune cells infiltration in TME, which efficiently inhibits tumor progression and significantly enhances anti-PD-1 therapy efficiency in SCC VII-bearing tumor xenograft. ADU@Fe-SP exerts antitumor effect in a STING-dependent manner by in vivo STING-knockout mice model. The efficiency of this immunotherapy strategy is also demonstrated in patient-derived xenograft model originating from oral cancer, showing great clinical potential.
研究领域:
肿瘤学
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免疫学
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生物技术
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Bin Wang,Maoping Tang,Ziwei Yuan,Zhongyu Li,Bin Hu,Xin Bai,Jinxian Chu,Xiaoyang Xu,Xue-Qing Zhang
Immunotherapy is emerging as a powerful tool for combating many human diseases. However, the application of this life-saving treatment in serious brain diseases, including glioma, is greatly restricted. The major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier (BBB) and achieving targeted delivery to specific cells once across the BBB. Ferritin, an iron storage protein, traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1 (TfR1) overexpressed on BBB endothelial cells. Here, we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse model. We fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering, and RGE fusion protein nanoparticles (RGE-HFn NPs) were identified as the best candidate. Furthermore, RGE-HFn NPs encapsulating a stimulator of interferon genes (STING) agonist ( [email protected] NPs) maintained stable self-assembled structure and targeting properties even after traversing the BBB. In the glioma-bearing mouse model, [email protected] NPs elicited a potent local innate immune response in the tumor microenvironment, resulting in significant tumor growth inhibition and prolonged survival. Overall, this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.
研究领域:
癌症生物学
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神经科学
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药学
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生物技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Xintao Gao,Yulan Yin,Shuai Liu,Kehong Dong,Jing Wang,Chuanlong Guo
Fucoidan (FU) is a natural polymer from marine organisms, which has been widely studied and applied in drug delivery. In this study, FU nanoparticles loaded with proanthocyanidins (PCs) (FU/PCs NPs) were prepared and their effect and mechanism in protecting cisplatin-induced acute kidney injury (AKI) were studied. The in vitro studies confirmed that FU/PCs NPs increased the antioxidant activity of free PCs and protected the death of human kidney proximal tubule (HK-2) cells induced by cisplatin. Further mechanism studies showed that FU/PCs NPs protected the mitochondrial damage induced by cisplatin, activated mitophagy, inhibited the release of mitochondrial DNA (mtDNA), and inhibited the cGAS/STING signal pathway. The in vivo results also indicated that FU/PCs NPs protected cisplatin-induced AKI, including inhibiting the increase of blood urea nitrogen (BUN) and serum creatinine (SCr) levels induced by cisplatin. The mechanism studies confirmed that cisplatin induced an increase in the expression of mitophagy-related protein Pink/Pakrin, mitochondrial mtDNA release and cGAS/STING expression in mice kidney tissues. Pre-administration of FU/PCs NPs further activated mitophagy, as well as inhibiting mtDNA release and cGAS/STING expression. In conclusion, our research proved the role of mitophagy-mtDNA-cGAS/STING signal was involved in cisplatin-induced AKI.
研究领域:
药理学
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肾病学
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分子生物学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Qiang Zhou,Meiyu Chang,Shuhan Guo,Yiming Zhang,Qiufang Qu,Qingnan Zhou,Zhiheng Li,Sanqiao Yao
Silicosis is a life-threatening occupational disease because of inhaling silica dust, leading to chronic inflammation, pyroptosis, and fibrosis. Unfortunately, it is still lacking effective pharmacological intervention currently. Honokiol ( HKL ), a natural extract with biological activity from Magnolia bark, is known for its antioxidant and anti-inflammatory biological effects. The current work aimed to investigate the therapeutic potential of HKL in mitigating silica-induced lung fibrosis and pyroptosis, particularly focusing on the cGAS/STING signaling pathway. The pulmonary pathological results shown in H&E and Masson’s trichrome staining images confirmed the protective effects of HKL on lung tissue structure. In addition, HKL significantly reduced lung inflammation, collagen deposition, and oxidative stress compared to mice in the silicosis group. HKL treatment also alleviated silica-induced pyroptosis by suppressing the activation of the cGAS/STING signaling pathway in lung tissues. Moreover, the in vitro experiments using J774A.1 macrophages demonstrated that HKL reduced pyroptosis and improved cell viability under exposure to silica combined lipopolysaccharide (LPS). These were attributed to HKL downregulating the activation of the cGAS/STING signaling pathway in pyroptotic J774A.1 cells induced by silica combined with LPS. Meanwhile, inhibition of STING signaling induced by DNase I significantly enhanced the protective effects of HKL on the inflammatory and pyroptotic processes induced by silica. Overall, HKL could attenuate silica-induced pyroptosis by modulating the cGAS/STING signaling pathway against pulmonary fibrosis. The current study offers a promising approach for treating silicosis and related inflammatory responses.
研究领域:
药理学
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肺病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
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IF 4.3
Shuai Liu,Xintao Gao,Yulan Yin,Jing Wang,Kehong Dong,Dayong Shi,Xiaochen Wu,Chuanlong Guo
Silk fibroin (SF) has excellent biocompatibility and biodegradability as a biomaterial. The purity and molecular weight distribution of silk fibroin peptide (SFP) make it more suitable for medical application. In this study, SFP nanofibers (molecular weight ∼30kD) were prepared through CaCl 2 /H 2 O/C 2 H 5 OH solution decomposition and dialysis, and adsorbed naringenin (NGN) to obtain SFP/NGN NFs. In vitro results showed that SFP/NGN NFs increased the antioxidant activity of NGN and protected HK-2 cells from cisplatin-induced damage. In vivo results also showed that SFP/NGN NFs protected mice from cisplatin-induced acute kidney injury (AKI). The mechanism results showed that cisplatin induced mitochondrial damage, as well as increased mitophagy and mtDNA release, which activated the cGAS-STING pathway and induced the expression of inflammatory factors such as IL-6 and TNF-α. Interestingly, SFP/NGN NFs further activated mitophagy and inhibited mtDNA release and cGAS-STING pathway. Demonstrated that mitophagy-mtDNA-cGAS-STING signal axis was involved in the kidney protection mechanism of SFP/NGN NFs. In conclusion, our study confirmed that SFP/NGN NFs are candidates for protection of cisplatin-induced AKI, which is worthy of further study.
研究领域:
生物材料
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药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
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IF 10.6
Hu Honglei,Zheng Shuting,He Chenxi,Zheng Yinfei,Wei Qiming,Chen Siwen,Wu Zede,Xu Yikai,Zhao Bingxia,Yan Chenggong
Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles “turned on” spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.
研究领域:
癌症研究
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放射肿瘤学
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免疫治疗
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纳米技术
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Changwei Zhang,Qinghui Cao,Yuanyu Li,Juan Lu,Sidong Xiong,Yan Yue
The induction of a robust CD8 + T cell response is critical for the success of an antiviral vaccine. In this study, we incorporated a STING agonist (SA) 2′3’-cGAMP into a previously developed exosome-based CVB3 viral myocarditis vaccine (Exo-VP1) to enhance its ability to induce CD8 + T cell responses and immunoprotection. Our results showed that compared to free SA adjuvant, exosome-mediated co-delivery (Exo SA -VP1) significantly enhanced SA uptake by dendritic cells (DCs) and more potently stimulated DC maturation. Immunization of mice showed that the Exo SA -VP1 vaccine-induced higher levels of CVB3-specific T cell proliferation and cytotoxicity, significantly increased the percentage of IFN-γ + CD8 + rather than CD4 + T cells, effectively reduced cardiac viral loads, attenuated myocarditis and improved survival in mice compared to the previous Exo-VP1 vaccine. Further investigation showed that Exo SA -VP1 significantly increased both the percentage and antigen cross-presentation capacity of splenic CD8 + DCs. Depletion of these CD8 + DCs by cytochrome C administration nearly abolished the advantage of Exo SA -VP1 in dominantly inducing IFN-γ + CD8 + cytotoxic T lymphocyte (CTL) production in immunized mice. Taken together, our results demonstrated the potential of Exo SA -VP1 as a promising candidate for anti-CVB3 vaccines and provide insights into immune-enhancing strategies aiming at augmenting antigen cross-presentation by DCs and enhancing potent CTL responses.
研究领域:
免疫学
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病毒学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Renchuan Liang,Feng Lin,Xuezhong Mo,Jie Long,Weizhong Tang,Tao Luo,Yunxi Huang
The susceptibility of colorectal cancer (CRC) cells to Fusobacterium nucleatum (F. nucleatum) infection pose significant challenges to CRC treatment and prevention. This study addresses these challenges by mobilizing cGAS/STING axis activation and F. nucleatum-specific targeting, thereby achieving a multimodal treatment strategy for reversing the immunosuppressive microenvironment (ITM) and achieving targeted anti-F. nucleatum therapy. Specifically, a hybrid nanoplatform CuPpIX@HM was engineered using Escherichia coli and tumor cell membranes encapsulating ultrasound (US) stimulation-responsive copper protoporphyrin IX (CuPpIX). This design enables the precise accumulation of the nanoplatform at tumor sites following oral administration. Notably, upon US activation, CuPpIX generates a high level of reactive oxygen species (ROS), selectively eradicating F. nucleatum and exerting potent antitumor effects. Meanwhile, bacterial membrane components activate the cGAS/STING signaling pathway, effectively reversing the ITM, enhancing systemic antitumor immunity. Importantly, CuPpIX@HM exerts minimal disruption to healthy intestinal microbiota and remarkably increases the level of probiotics. In both orthotopic and liver metastasis, CRC models demonstrated that this strategy could significantly inhibit tumor growth and metastasis. Collectively, our study presents a highly targeted multimodal nanotherapy that holds strong potential to improve CRC treatment outcomes through the precision modulation of F. nucleatum and immune activation.
研究领域:
纳米医学
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免疫治疗
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微生物学
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肿瘤学
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生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yechun Jiang,Weinan Zhang,Litao Liu,Yayun Wu,Weiqi Li,Jun Liang,Hui Shen,Shu Fang,Xianyu Huang,Zhaoyou Chu,Lingling Xu,Haisheng Qian
The immunosuppressive niche of the breast cancer microenvironment and the vascular basement membrane significantly hinder the efficacy of nanoparticle-based antitumor immunotherapy delivered via the vascular system. This study describes the design of a puncture-delivered tumor implant, utilizing a photo-cross-linked gelatin methacryloyl hydrogel as the matrix, loaded with Cu0.5Mn2.5O4 nanoparticles (CMO NPs) and monomethyl fumarate (MMF), enabling the sustained release of nanoparticles through matrix metalloproteinase-responsive degradation. Mechanistically, CMO NPs induce cuproptosis and immunogenic cell death (ICD) in tumor cells, while synergizing with MMF to trigger substantial mtDNA release into the cytosol. Subsequently, the liberated mtDNA synergizes with Mn2+ to activate the cGAS-STING signaling pathway, which cooperates with ICD to enhance CD8+ T cell infiltration and increase the levels of related inflammatory factors in the breast tumor microenvironment. Notably, the implant significantly enhances the efficacy of αPD-1 therapy by modulating PD-L1/PD-1 expression. In summary, the implant designed in this study provides a practical strategy for nanoparticle delivery and immunotherapy of breast cancer.
研究领域:
生物材料
·
纳米医学
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免疫学
·
肿瘤学
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药物递送
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生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zhang Cong,Song Yingying,Chen Liang,Chen Peng,Yuan Ming,Meng Yan,Wang Qi,Zheng Guohua,Qiu Zhenpeng
Urolithin A (UroA) is one of the primary intestinal metabolites of ellagitannins, showing translational potential as a nutritional intervention in humans. Mounting evidence suggests that fructose consumption contributes to the progression of chronic kidney disease (CKD) that manifests in hyperuricemic nephropathy, renal inflammation, and tubulointerstitial injury. Here, we investigated the efficacy of UroA in alleviating fructose-induced hyperuricemic nephropathy in mice. Uric acid-exposed human kidney-2 (HK-2) cells were utilized for in vitro mechanism validation. Histopathological staining, immunoblotting, and transmission electron microscope were performed for the mechanistic investigations. Our results revealed that UroA ameliorated fructose-induced hyperuricemic nephropathy in mice. The histopathologic assessment showed that UroA attenuated tubular hypertrophy and dilation, glomerular basement membrane thickening, and collagen deposition in the kidney of fructose-fed mice. Mechanistically, UroA treatment impaired STING-NLRP3 activation, resulting in reduced production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, UroA exhibited a scavenging effect against reactive oxygen species (ROS) and restored fructose-impaired PINK1/Parkin-mediated mitophagy in nephropathic mice. Furthermore, the inhibitory effect of UroA in STING-NLRP3 activation was impaired after Parkin gene silencing in HK-2 cells. Together, this study suggests that UroA alleviates fructose-induced hyperuricemic nephropathy by promoting Parkin-dependent mitophagy, thereby suppressing STING-NLRP3 axis-mediated inflammatory response. Thus, dietary supplementation with UroA or ellagitannins-rich foods may serve as a promising intervention to prevent CKD progression.
研究领域:
药理学
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肾病学
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分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Lei Diao,Yang Ma,Liping Wang,Peng Li,Bin Zhang,Weijing Meng,Jingzeng Cai,Yan Meng,Yuxun Zhou,Jingying Zhai,Huijie Chen
Thiacloprid (THI) is a synthetic insecticide, the misuse is targeted chiefly to control aphid pest species in orchards and vegetables. Melatonin (MET) is a hormone that plays crucial physiological roles in anti-inflammatory capacities of fish. We explored the function of MET (100 μM) to mitigate the toxicity induced by THI (20 μM) in lymphocytes. Our results indicate that THI led to a notable rise in lymphocyte mortality. Lymphocytes exposed to THI exhibited a heightened incidence of pyroptosis, accompanied by upregulation in expression associated with pyroptosis (NLRP3, GSDMEA, and IL-18). Meanwhile, THI exposure led to a decrease in lymphocyte mitochondrial membrane potential, an increase in mtROS levels, and a reduction in intracellular ATP, DNA, and NADPH/NADP+ levels, indicating an imbalance in the mitochondrial metabolism within the lymphocytes. Additionally, these effects were reversed by MET treatment, where MitoQ treatment showed that the suppression of mtROS reduced the lymphocyte pyroptosis caused by THI via the mtROS/cGAS-STING/NF-κB axis. Importantly, MET provided defense against the immunotoxic impacts of THI by ameliorating pyroptosis and enhancing anti-inflammatory capability via the mtROS/cGAS-STING/NF-κB axis. Our research potentiates the safeguarding of cultured fish from biological hazards caused by THI and highlights the valuable application of MET in common carp.
研究领域:
鱼类生理学
·
环境毒理学
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免疫学
✓ 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）