Cell Reports Physical Science
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2024
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IF 7.9
Xu Wang,Tao Han,Xiwei Jiang,Sicen Lin,Xinyu Lou,Xianbao Shi,Zhenguo Cheng,Zhonggui He,Hongzan Sun,Funan Liu,Jin Sun,Mengchi Sun
The application of oncolytic adenoviruses (Ads) is hampered by the inability to target tumor sites via intravenous injection as well as insufficient intratumoral viral replication efficiency. To overcome these challenges, we report bimetallic nanodot-Ad chimeras (Ads@Gd/Fe-NDs) that enable targeted delivery and enhanced Ad replication via cooperativity of autophagy and ferroptosis against tumors. The systemic delivery of Ads@Gd/Fe-NDs leads to a high accumulation of Ads in tumors. Intratumorally released Fe 3+ from chimeras induces ferroptosis within cancer cells, generating reactive oxygen species and activating cellular autophagy. The excessive enrichment of autophagy-induced autophagosomes elevates Ad replication efficiency in infected tumor cells, further resulting in overactivation of autophagy and amplifying autophagy-dependent ferroptosis. In addition, Gd 3+ from Ads@Gd/Fe-NDs is released in response to the tumor microenvironment, serving intratumoral MRI in preclinical tumor-bearing mouse models. Collectively, such a nanodot-oncolytic virus chimera represents a potent translational platform for cancer theranostics.
研究领域:
癌症研究
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纳米技术
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病毒治疗
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诊疗学
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
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2024
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IF 6.7
Fei Wang,Xiaoyan Li,Zhining Liu,Xin Zhao,Changxu Zhao,Guangzheng Hou,Qiqi Liu,Xin Liu
Human respiratory adenovirus (ADV) is a highly infectious respiratory virus with potential for pandemics. There are currently no specific drugs to treat ADV worldwide, so early rapid detection of ADV infection is essential. In this study, we developed an innovative magnetic-optical triple-mode lateral flow immunoassay (LFIA) using magnetic quantum dots as immunomarkers. This novel approach addresses the need for rapid and accurate ADV detection, allowing for multimodal quantitative/semiquantitative analysis of magnetic, fluorescent, and visible signals within a mere 15 min. The lower limit of detection (LOD) for magnetic, fluorescent, and visual signals was determined to be 5.6 × 103, 1.2 × 103, and 1.95 × 104 copies/mL, respectively. The detection range for ADV using this approach was 1.2 × 103–5 × 107 copies/mL. Additionally, semiquantitative analysis, which is user-friendly and does not necessitate specialized equipment, was successfully implemented. Notably, seven respiratory viruses showed no cross-reactivity with the generated LFIA test strips. The intrabatch repeatability exhibited a coefficient of variation (CV) of less than 5%, while the interbatch repeatability had a CV of less than 15%. Furthermore, recovery values ranged from 95% to 106.8% for samples analyzed concurrently with dual signals at the same spiking concentration. The assay developed in this study boasts a wide detection range and exceptional sensitivity and specificity. This technique is exceptionally well-suited for on-site rapid detection, with the potential for personal self-testing and early ADV infection diagnosis. Its versatility extends to a broad array of application scenarios.
研究领域:
医学诊断
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病毒学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2015
·Vol. 3
·期 43
·8486-8491
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IF 4.726
Jinfeng Xing,Ling Liu,Xiaoyan Song,Yuanyuan Zhao,Ling Zhang,Xianzi Dong,Feng Jin,Meiling Zheng,Xuanming Duan
Hydrogels with precise 3D configuration (3D hydrogels) are crucial for biomedical applications such as tissue engineering and drug delivery, which require the improvement of the spatial resolution on both the microscopic and the nanometric scale. In this study, a water soluble two-photon polymerization (TPP) initiator (WI) with high initiating efficiency was prepared by using a poloxamer (PF127) to encapsulate 2,7-bis(2-(4-pentaneoxy-phenyl)-vinyl)anthraquinone via a hydrophilic–hydrophobic assembly. The threshold energy for WI was 6.29 mW at a linear scanning speed of 10 μm s−1, which was much lower than those reported previously. A lateral spatial resolution of 92 nm was achieved as the resolution breakthrough of 3D hydrogels. Finally, the microstructure with high accuracy simulating the morphology of adenovirus was fabricated at the laser power close to the threshold energy of TPP, further demonstrating the ultrahigh resolution of 3D hydrogels.
研究领域:
生物医学工程
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组织工程
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药物递送
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2019
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IF 8.355
Chi Zhang,Yi Li,Jie Li
Waterborne human viruses, with ubiquitous prevalence in aquatic environments, extremely low infectious doses, and high resistance to common disinfection processes, pose a substantial threat to human health. Herein, for the first time, a photocatalytic membrane reactor (PMR) driven by visible light emitting diodes (Vis-LEDs) was applied for effective water disinfection of human adenoviruses. The photocatalyst used in the PMR was selected to be a metal-free heterojunction (named as CNO) with the advantages of visible-light-response, efficient virucidal effects, green properties and easy recovery via microfiltration. The disinfection performance of the Vis-LED PMR towards human adenoviruses was improved by adjusting operation with response surface methodology (RSM). Based on twenty sets of operating data, a semi-empirical model was established with a high accuracy of R 2 = 0.9622 for predicting the final adenovirus inactivation after 300-min operation. The optimal operating solution was found to be 5.00-log MPN/mL, 320.30 mg/L and 502.65 min for initial virus concentration (IVC), photocatalyst loading (PL) and hydraulic retention time (HRT), respectively. Under the optimized operation, all human adenoviruses were completely inactivated without regrowth, accompanied by severe damage to capsids, within 600 min in the Vis-LED PMR. In addition, the CNO photocatalyst could be retained inside the reactor via low-energy microfiltration with excellent recovery (99.9 wt%) but without obvious chemical or structural changes. Our work can offer a simple, effective, economical and eco-friendly water disinfection device against resistant pathogenic microbes, with controllable efficiency by facilely varying operating solutions.
研究领域:
环境科学
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公共卫生
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生物工程
✓ 已验证
DOI
高影响因子
MICROCHEMICAL JOURNAL
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2023
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IF 4.8
Xiaoyan Li,Yang Qi,Changxu Zhao,Fei Wang,Yanlei Ding,Guangzheng Hou,Pengcheng Cao,Zhe Zhou,Qiqi Liu
Sensitivity and accuracy are the key performance metrics for evaluating immunochromatographic assay (ICA). In this study, we have developed a quantum dot nanobeads-based dual-channel fluorescent ICA (QBs-DICA) designed for the sensitive and accurate detection of both influenza A virus (IAV) and human adenovirus (ADV) antigens. Following systematic assay optimization, we achieved a remarkable improvement in sensitivity, with gains of up to two orders of magnitude at the best. To enhance signal accuracy for IAV and ADV testing, we implemented a temperature-controlled dual-channel detector during sample incubation and the chromatographic process, resulting in an approximate increase of 34.2% and 36.7%, respectively. The Limit of Detection (LOD) for IAV and ADV testing was robustly established at 165 copies/mL and 805 copies/mL, respectively. Furthermore, in the case of IAV-spiked and ADV-spiked samples, we achieved consistently high recoveries ranging from 94.5% to 104.8% and 94.7% to 106.4%, with impressively low coefficients of variation (CV) of below 7.16% and 6.25%, respectively. Our established QBs-DICA system has exhibited a remarkable enhancement in both sensitivity and accuracy, making it exceptionally well-suited for supporting the rapid advancement of clinical diagnosis and treatment strategies.
研究领域:
医学诊断
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病毒学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Chi Zhang,Wei Xiong,Yi Li,Li Lin,Xinyi Zhou,Xinyan Xiong
Viruses transmitted by water have raised considerable concerns for public health. A novel memory photocatalyst of g-C 3 N 4 /WO 3 /biochar was successfully developed for effective inactivation of human adenoviruses (HAdVs) in water, in which WO 3 as an electron-storage reservoir and biochar as an electron shuttle is employed to synergistically improve photocatalytic activity of g-C 3 N 4 . The tertiary composite exhibited continuous photocatalytic performance for HAdVs inactivation without regrowth in water under light-dark cycles, i.e., ∼3.9-log inactivation under 6-h visible light irradiation and an additional ∼1.1-log inactivation under the following 6-h dark. The enhanced virucidal mechanism was attributed to the heterojunction formation and especially the electron-transfer pathway switching via biochar incorporation, contributing to electron transfer and storage in the light phase and then electron release in the dark phase, along with obviously increased generation of the virus-killing •OH radicals under light-dark cycles.
研究领域:
环境科学
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病毒学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2025
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IF 3.6
Lanlan Cheng,Jie Zhang,Yungai Xiang,Li Tan
Spontaneous abortion (SA) refers to the loss of a pregnancy without external intervention. The runt-related transcription factor 3 (RUNX3) is associated with gestational disorders in view of previous studies. However, RUNX3 has not been reported in SA. RUNX3 is significantly upregulated in the placental villi of abortion patients based on the GSE123719 microarray data. Herein, we further validated and found that the expression of RUNX3 in placental villi of SA women was higher than those of induced abortion (IA) women. In vitro , we constructed human RUNX3 overexpression or interference adenovirus vectors to modulate RUNX3 expression in trophoblast cells. Our findings revealed that RUNX3 overexpression accelerated trophoblast cell ferroptosis, while RUNX3 knockdown alleviated erastin-induced ferroptosis. Subsequently, the dual luciferase reporter assay was performed to confirm that RUNX3 bound to the GDF15 promoter to transcriptionally repress GDF15 transcriptional activity. Importantly, GDF15 attenuated the pro-ferroptosis effects of RUNX3 on HTR-8/SVneo cells. In vivo , mouse RUNX3 interference adenovirus vectors were used to silence RUNX3 in mice. The results presented that the reduction of RUNX3 inhibited embryo adsorption rate in SA mice, involving ferroptosis and the interaction between RUNX3 and GDF15. Taken together, this study established that RUNX3 advanced SA progression by enhancing trophoblast ferroptosis via transcriptionally repressing GDF15. These findings may provide novel therapeutic strategies for SA management.
研究领域:
分子生物学
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细胞生物学
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生殖医学
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遗传学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Guoqing Wang,Kai Wu,Zongliang Zhang,Yongdong Chen,Yanfang Li,Xiaoshuang Jiang,Licong Liang,Yiliu Yang,Hongsong Fan,Jing Sun,Aiping Tong,Fang Lu
Retinoblastoma (RB) is the most common primary ocular malignancy in children, arising from the developing retina. While higher doses of local chemotherapy have improved tumor control, concerns regarding retinal toxicity and the development of chemoresistance remain significant. Oncolytic adenovirus (OA) presents a promising therapeutic approach for RB, but rapid clearance often limits its therapeutic effects. In this study, we engineered a genetically modified OA derived from human adenovirus 5 (Ad5), designed to selectively target and lyse RB cells. The combination of OA with low-dose melphalan demonstrates an enhanced antitumor effect, while minimizing retinal toxicity. In vitro and in vivo experiments demonstrated that melphalan significantly enhanced the antitumor effect of OA and extended ocular survival. More importantly, we developed a biocompatible injectable hydrogel delivery system based on the covalent coupling of collagen and aldehyde-modified cyclodextrin, which effectively enhances the loading efficiency of melphalan and enables sustained co-delivery of OA and melphalan. The mouse RB tumor model confirmed that this hydrogel system (OA-Mel@CCA) achieved localized and sustained delivery of both therapeutics, effectively controlling tumor growth and preventing brain metastasis. Additionally, retinal structure and function were notably preserved in mice treated with OA-Mel@CCA, with no observed retinal toxicity. These findings suggest that the injectable hydrogel-based co-delivery of melphalan and oncolytic adenovirus could represent a promising strategy for RB treatment.
研究领域:
肿瘤学
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眼科
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纳米医学
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药物递送
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基因治疗
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转化医学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Hanwei Huang,Mingyang Liu,Mengchi Sun,Shijie Duan,Siwei Pan,Pengfei Liu,Zhenguo Cheng,Onder Ergonul,Füsun Can,Zhenning Wang,Zhiqing Pang,Funan Liu
Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Xiaoyan Li,Changxu Zhao,Guangzheng Hou,Zhihua Sun,Xiaomei Liu,Yanlei Ding,Yi Fang,Qiqi Liu
Introduction: The rapid and precise differential diagnosis of respiratory diseases is crucial to impede the spread of the viruses, considering the substantial demand resulting from frequent co-infectionsMethod: A quantum dot nanobeads (QBs)-based multiplex fluorescence lateral flow immunoassay (QBs-based MF-LFA) biosensor was developed. The MF-LFA biosensor enabled simultaneous and sensitive quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Adenovirus (ADV), and Influenza A Virus (IAV), boasting low limit of detection (LOD) of 56, 120, and 41 copies/mL, respectively. Compared to colloidal gold LFA, the LOD was improved by 200, 417, and 1220 times, respectively, while maintaining sensitivity comparable to PCR techniques.Result and discussions: The biosensor provided results within 20 minutes, exhibited good reproducibility, and boasted high accuracy with recoveries ranging from 96% to 105%. Additionally, the biosensor had a shelf life of up to 8 months, attributed to the use of freeze-dried probes with minimal water content, ensuring enhanced stability. Clinical samples of SARS-CoV-2, ADV and IAV infections were tested, the results were consistent with both PCR testing and clinical diagnostic tests. This highlights the considerable potential of our biosensor for early and rapid differential detection of respiratory viruses.
研究领域:
医学诊断
·
生物传感
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LABORATORY INVESTIGATION
·
2023
·
IF 5
Zhiguang Chen,Haibin Zhao,Lingshuai Meng,Shengwei Yu,Zhenning Liu,Jinqi Xue
Fracture healing is a complex physiological process in which angiogenesis plays an essential role. Microfibril-associated glycoprotein-2 (MAGP2) has been reported to possess a proangiogenic activity via integrin αvβ3, yet its role in bone repair is unexplored. In this study, a critical-sized femoral defect (2 mm) was created in mice, followed by the delivery of an adenovirus-based MAGP2 overexpression vector or its negative control at the fracture site. At days 7, 14, 21, and 28 postfracture, bone fracture healing was evaluated by radiography, micro–computed tomography, and histopathologic analysis. Adenovirus-based MAGP2 overexpression vector–treated mice exhibited increased bone mineral density and bone volume fraction. MAGP2 overexpression contributed to an advanced stage of endochondral ossification and induced cartilage callus into the bony callus. Further analysis indicated that MAGP2 was associated with enhanced angiogenesis, as evidenced by marked MAGP2 and integrin αvβ3 costaining and increased levels of endothelial cell markers such as endomucin and CD31, as well as elevated phosphorylation of protein tyrosine kinase 2 (PTK2) and AKT serine/threonine kinase 1 (AKT) in the callus. In vitro , recombinant human MAGP2 treatment enhanced the viability, migration, and tube formation ability of human microvascular endothelial cells, which was partially reversed by integrin αvβ3 inhibition or MK-2206, a specific AKT inhibitor. Inhibition of integrin αvβ3 abolished MAGP2-induced PTK2 and AKT activation. Taken together, our data provide the first evidence that MAGP2 promotes angiogenesis and bone formation by activating the integrin αvβ3/PTK2/AKT signaling pathway.
研究领域:
骨科
·
生物学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Fengling Feng,Haibin Hao,Jin Zhao,Yanjun Li,Ying Zhang,Ruiting Li,Ziyu Wen,Chunxiu Wu,Minchao Li,Pingchao Li,Ling Chen,Ruikang Tang,Xiaoyu Wang,Caijun Sun
Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.
研究领域:
病毒学
·
免疫学
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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