具有磁共振T1-T2双激活效应的快速响应智能纳米平台用于酸性微环境成像研究
A rapid-response smart nanoplatform with dual T1-T2 activation for acidic microenvironment imaging
骆孟 1郭嘉婧 2朱仪 2邓佳丽 3卢宏伟 4李蕾 1王中领2
作者信息
- 1. Department of Medical Imaging,The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People's Hospital of Lianyungang,Lianyungang 222000,China
- 2. Department of Radiology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China
- 3. Department of Radiology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,China
- 4. Department of Biomedical Engineering,College of Engineering,Shantou University,Shantou 515063,China
- 折叠
摘要
通过靶向酸性肿瘤微环境(TME)的MR纳米探针为体内癌症成像提供了巨大潜力.然而,其成像精准性受肿瘤部位延迟响应及不可控的背景噪声限制.在此研究中,我们构建了一种酸性微环境响应纳米探针SPIO@ZIF-8@Gd(SZG),该探针可快速响应于肿瘤酸性微环境变化,具有T1-T2双激活效应.其在生理条件下T1和T2信号对比度降低,而靶向TME,沸石咪唑酯骨架-8(ZIF-8)层将快速分解,释放Gd3+(T1WI),并暴露SPIO核心(T2WI),从而实现T1和T2双激活效应.与之前报道的T1-T2双响应纳米探针相比,SZG纳米探针在酸性条件下30分钟可呈现出显著的"双激活"效应,4小时后达到激活峰值.此外,其弛豫时间与pH值间具有良好的相关性.当SZG纳米探针与"双对比增强减影(DESI)"联合使用,可将正常组织与病变组织间的对比度差异提高10倍,这显著高于传统的T1/T2单模对比剂.总体而言,以上研究结果显示通过抑制背景噪声的T1-T2双激活成像策略,为精准肿瘤恶性程度鉴别、早期检测和准确分级提供了新思路.
Abstract
Acidity-activatable magnetic resonance ima-ging(MRI)nanoprobes offer great potential for in vivo cancer imaging by targeting the acidic tumor microenvironment(TME).However,their effectiveness is limited by the delayed response at tumor sites and uncontrollable background noise,compromising imaging accuracy and reliability.Herein,an acidic TME-responsive nanoprobe,SPIO@ZIF-8@Gd(SZG),with dually activatable T1 and T2 MR signals is shown for acidity-selective contrast enhancement in a rapid response manner.It shows decreased T1 and T2 contrast intensity in normal physiological conditions.Once targeting acidic TME,the zeolitic imidazolate framework-8(ZIF-8)layer undergoes instantaneous decomposition,releasing Gd3+(T1-weighted),and exposing the inner SPIO(T2-weighted)core,thereby se-quentially recovering the signals.Compared to previously re-ported T1-T2 nanoprobes,SZG demonstrates noticeable"dual activation"after just 30 min and reaches its peak 4 h after acid incubation.Additionally,it shows an excellent"acidity cor-relation"between relaxation times and pH values.When the SZG nanoprobe is used combined with"dual-contrast en-hanced subtraction(DESI)",the contrast difference between diseased and normal tissue can be increased by 10 times,which is significantly higher than traditional single-mode T1/T2 contrast agents.Collectively,these findings demonstrate a rapid imaging strategy of dual-activation MR imaging of the acidic TME and simultaneous background suppression,thus paving the way for precise tumor malignancy differentiation,early tumor detection,and accurate tumor grading.
关键词
rapid response/zeolitic imidazolate framework-8/dual T1-T2 activation/acidic tumor microenvironmentKey words
rapid response/zeolitic imidazolate framework-8/dual T1-T2 activation/acidic tumor microenvironment引用本文复制引用
出版年
2024
NETL
NSTL
万方数据