A rapid-response smart nanoplatform with dual T_(1)-T_(2) activation for acidic microenvironment imaging  

具有磁共振T_(1)-T_(2)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

作　　者：Meng Luo Jiajing Guo Yi Zhu Jiali Deng Hongwei Lu Lei Li Zhongling Wang 骆孟;郭嘉婧;朱仪;邓佳丽;卢宏伟;李蕾;王中领

机构地区：[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]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

出　　处：《Science China Materials》2024年第12期4101-4110,共10页中国科学（材料科学）（英文版）

基　　金：supported by the National Natural Science Foundation of China (82272057 and 32301160)。

摘　　要：Acidity-activatable magnetic resonance imaging(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 T_(1) and T_(2) MR signals is shown for acidity-selective contrast enhancement in a rapid response manner.It shows decreased T_(1) and T_(2) contrast intensity in normal physiological conditions.Once targeting acidic TME,the zeolitic imidazolate framework-8(ZIF-8)layer undergoes instantaneous decomposition,releasing Gd^(3+)(T_(1)-weighted),and exposing the inner SPIO(T_(2)-weighted)core,thereby sequentially recovering the signals.Compared to previously reported T_(1)-T_(2) 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 correlation”between relaxation times and pH values.When the SZG nanoprobe is used combined with“dual-contrast enhanced subtraction(DESI)”,the contrast difference between diseased and normal tissue can be increased by 10 times,which is significantly higher than traditional single-mode T_(1)/T_(2) 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.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T_(1)-T_(2)双激活效应.其在生理条件下T_(1)和T_(2)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Gd^(3+)(T_(1)WI),并暴露SPIO核心(T_(2)WI),从而实现T_(1)和T_(2)双激活效应.与之前报道的T_(1)-T_(2)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T_(1)/T_(2)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T_(1)-T_(2)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.

关 键 词：rapid response zeolitic imidazolate framework-8 dual T_(1)-T_(2)activation acidic tumor microenvironment 

分 类 号：R318[医药卫生—生物医学工程] TB383.1[医药卫生—基础医学]