促氧化抗肿瘤药增敏的长时程近红外化学发光体系构建及其肿瘤精准成像应用
结题报告
批准号:
81973292
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
张群林
依托单位:
学科分类:
药物分析
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
张群林
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中文摘要
肿瘤精准成像对于早期诊断至关重要。化学发光成像无需外部光源,在组织穿透、空间分辨和信噪比上具有优势,但存在肿瘤特异性低、发光时间短、发射波长受限等缺点。本项目基于促氧化抗肿瘤药(POD)可提高肿瘤细胞活性氧水平增敏化学发光,拟构建肿瘤特异识别和发光增敏功能一体化的载药纳米水凝胶探针,发展长时程近红外化学发光成像分析方法:(1)利用化学发光能量共振转移原理,构建化学发光与近红外量子点之间能量转移通道,建立高发光效率近红外化学发光体系。(2)设计鲁米诺和量子点键合于壳聚糖长链,延长发光探针体内循环时间;自组装合成纳米水凝胶并包载POD,调控活性氧和POD在凝胶相的缓慢扩散,实现长时程化学发光,提高成像分析准确度。(3)阐明POD增敏的纳米探针特异识别肿瘤细胞的原理与规律,高分辨成像区分正常细胞和肿瘤细胞,最终应用于微小肿瘤精准成像。预期成果将为非标记的肿瘤高特异性光学成像提供新手段和理论基础。
英文摘要
Precise tumor imaging is critical for an early diagnosis of cancer. Chemiluminescence (CL) imaging has many advantages, including no externally generated source of energy, great tissue penetration, high spatial resolution and high signal-to-noise ratio. However, most known CL reactions exhibit low specificity, flash-type light emissions and restricted emission wavelength, which hamper their applications in precise tumor imaging. In the present proposal, based on the fact that pro-oxidant anticancer drug (POD) can enhance the CL intensity by increasing the levels of reactive oxygen species in tumor, a POD-loaded nanohydrogel probe with the characteristics of tumor specificity and CL sensitization is developed for long-lasting near-infrared (NIR) CL imaging. (1) The NIR CL system with high luminous efficiency is designed by chemiluminescence resonance energy transfer (CRET) between CL and NIR quantum dots. (2) Luminol and quantum dots are conjugated with chitosan in order to prolong the cycle time of luminescent nanoprobe in vivo. Meanwhile, self-assembly nanohydrogels loaded with POD can adjust the slow diffusion of ROS and POD in nanohydrogels, thereby forming a long-lasting CL system and improving the accuracy of imaging. (3) The principle and rule of POD-sensitized nanoprobe for specific tumor identification are demonstrated, which enables the high-resolution discrimination between normal cells and tumor cells. The developed nanoprobe has the potential for precise micro tumor imaging. The expected results will provide a new approach and theoretical basis for label-free specific imaging of tumors.
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DOI:10.1021/acs.analchem.0c01147
发表时间:2020-10-06
期刊:ANALYTICAL CHEMISTRY
影响因子:7.4
作者:Fang, Hufeng;Yu, Huan;Ma, Quanbao
通讯作者:Ma, Quanbao
DOI:10.1021/acsami.3c09320
发表时间:2023-08
期刊:ACS applied materials & interfaces
影响因子:9.5
作者:Haifeng Lu;Qi Lu;Hongwu Sun;Zhongkun Wang;Xiang Shi;Yuling Ding;Xiang Ran;Jing Pei;
通讯作者:Haifeng Lu;Qi Lu;Hongwu Sun;Zhongkun Wang;Xiang Shi;Yuling Ding;Xiang Ran;Jing Pei;
基于多位点微透析和血关节囊屏障开放研究三妙丸中牛膝"引药下行"的物质基础和作用机理
  • 批准号:
    81274106
  • 项目类别:
    面上项目
  • 资助金额:
    70.0万元
  • 批准年份:
    2012
  • 负责人:
    张群林
  • 依托单位:
微透析-液相色谱-纳米化学发光在线动态分析新技术应用于黄酮药动学的研究
  • 批准号:
    30973674
  • 项目类别:
    面上项目
  • 资助金额:
    30.0万元
  • 批准年份:
    2009
  • 负责人:
    张群林
  • 依托单位:
国内基金
海外基金