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铁基纳米酶调控细胞氧化—还原环境与白血病耐药

项目来源

国家重点研发计划(NKRD)

项目主持人

张宇

项目受资助机构

东南大学

立项年度

2017

立项时间

未公开

项目编号

2017YFA0205502

项目级别

国家级

研究期限

未知 / 未知

受资助金额

730.00万元

学科

纳米科技

学科代码

未公开

基金类别

“纳米科技”重点专项

关键词

纳米酶 ; 急性髓系白血病 ; 氧化铁 ; 普鲁士蓝 ; 活性氧 ; Nanoenzyme ; Acute myeloid leukemia ; Iron oxide ; Prussian blue ; ROS

参与者

马明；窦骏；王进科

参与机构AI

东南大学

项目标书摘要：本课题成功完成了氧化铁纳米酶活性测量的国家标准的研制，已通过终审并获批准备发布；成功实现了普鲁士蓝纳米酶从40 mL体系逐级放大到3 L、10 L、50 L的宏量制备和质量控制；完成了普鲁士蓝纳米酶标准物质的研制。我们还开发了2 种高效介导AML 细胞基因转染的新型核酸载体(阳离子化多糖纳米粒和阳离子化磁性纳米颗粒核酸转染载体)。构建了尺寸为20纳米的AML耐药细胞特异性靶向磁性纳米探针，完成了AML细胞磁捕获微流控检测芯片的设计加工，完成了微流控芯片测定的荧光定量检测仪研制。另外，我们还成功构建了2种可用于细胞内 ROS调控的新型纳米酶：一种是具双靶向AML细胞的载药普鲁士蓝纳米酶，另一种是超小Pt纳米颗粒复合的靶向铁基纳米酶，两者都能实现对AML细胞的有效靶向杀伤。我们还研究发现：体外氧化铁纳米酶联合阿糖胞苷能表现出比阿糖胞苷单药更强地促进白血病癌干细胞(LSCs)凋亡；体内阿糖胞苷与氧化铁纳米酶联合用药对荷急性髓系白血病(AML)小鼠有更强的治疗效果。

Application Abstract: This project has successfully completed the development of the national standard for the measurement of iron oxide nanoenzyme activity.The macroscopical preparation and quality control of Prussian blue nanoenzyme were successfully achieved by scaling up from 40 mL system to 3 L,10 L and 50 L.The standard material of Prussian blue nanoenzyme was developed.We also developed two novel nucleic acid vectors(cationic polysaccharide nanoparticles and cationic magnetic nanoparticle nucleic acid transfection vectors)that efficiently mediate gene transfection of AML cells.An AML drug-resistant cell specific targeted magnetic nanoprobe with a size of 20 nm was constructed,the design and processing of AML cell magnetic capture microfluidic detection chip was completed,and the development of fluorescence quantitative detector for microfluidic measurement was completed.In addition,we have successfully constructed two novel nanoenzyme that can be used for intracellular ROS regulation:one is a drug-carrying Prussian blue nanoenzyme with double-targeted AML cells,and the other is a composite iron-based nanoenzyme with ultra-small Pt nanoparticles,both of which can effectively target and kill AML cells.We also found that in vitro ferric oxide nanoenzyme combined with cytosine cytosine could promote the apoptosis of leukemia cancer stem cells(LSCs)more strongly than cytosine cytosine monotherapy.The combination of cytarabine and ferric oxide nanoenzyme in vivo has a stronger therapeutic effect on mice with acute myeloid leukemia(AML).

项目受资助省

江苏省

联系人信息

张宇：zhangyu@seu.edu.cn

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  • 1.Rapid Quantitative Detection of Salmonella spp. via Magnetic Beads-based Fluorescent Lateral Flow Immunoassay

    • 关键词：
    • Immunology;Mechanics;Diagnosis;Fluorescence;Salmonella;Biochemical characteristics;Diagnostic tools;Disease outbreaks;Experimental conditions;Lateral flow immunoassay;Quantitative detection;Rapid detection;Reference strains
    • Zhuang, Linlin;Gong, Jiansen;Ji, Yongxin;Gu, Ning;Zhang, Yu
    • 《19th IEEE International Conference on Nanotechnology, NANO 2019》
    • 2019年
    • July 22, 2019 - July 26, 2019
    • Estrada do Istmo, Lote 3, Cotai Strip, Macau, China
    • 会议

    Polymerase chain reaction (PCR) plays an increasingly important role in microbial detection. However, the existing methods are difficult to be widely applied due to factors such as instruments, reagents, and experimental conditions. In this study, we developed a robust and reliable fluorescent lateral flow immunoassay combined with polymerase chain reaction (PCR-LFIA) based on magnetic beads purification for rapid detection of Salmonella app. The PCR-LFIA assay can avoid false positives caused by primer dimers. The sensitivity of PCR-LFIA method was 6×100 CFU/mL of Salmonella pure culture or 6×102 CFU/mL of artificially spiked chicken faeces. The specificity of PCR-LFIA assay was verified by eighteen Salmonella and non-Salmonella reference strains. Six of the eighty-five (7.1%) samples collected were positive by PCR-LFIA assay and the results were further confirmed by biochemical characteristics. This assay allows quantitative detection of Salmonella with a cutoff value of 175 and can be completed in 80 minutes. In conclusion, the optimized PCR-LFIA method can potentially serve as an effective diagnostic tool for timely response to disease outbreaks. © 2019 IEEE.

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