文章摘要
铁基MOF纳米探针在乳腺癌光动力增敏铁死亡及MR激活成像中实验研究
Experimental Study of Iron-based MOF Nanoprobe in Photodynamically Sensitized Ferroptosis and MR Activation Imaging of Breast Cancer
投稿时间:2024-01-12  修订日期:2024-01-12
DOI:
中文关键词: 乳腺癌  MR成像  铁死亡  光动力治疗  增敏
英文关键词: Breast cancer  MRI imaging  Ferroptosis  Photodynamic therapy  Sensitization
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
作者单位邮编
朱仪 上海交通大学医学院附属第一人民医院 200080
邓佳丽 上海理工大学健康科学与工程学院 
王静怡 上海理工大学健康科学与工程学院 
郭嘉婧 上海交通大学医学院附属第一人民医院 
丁心怡 上海交通大学医学院附属第一人民医院 
王中领* 上海交通大学医学院附属第一人民医院 200080
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中文摘要:
      目的:探讨肿瘤酸性微环境响应Fe-MOF纳米探针对乳腺癌光动力增敏铁死亡及其体外MR T1激活效应。方法:制备Fe-MOF纳米探针,用透射电子显微镜(Transmission Electron Microscope, TEM)及原子力显微镜(Atomic Force Microscope, AFM)对其形态进行表征;采用3,3'',5,5''-四甲基联苯胺(TMB)及5,5''-二硫双(2-硝基苯甲酸)(DTNB)评价其在溶液水平ROS生成及GSH消耗能力;通过细胞毒性实验(MTT)测定纳米探针在暗毒性及光毒性条件下对4T1乳腺癌细胞的光动力增敏铁死亡的效能;将4T1细胞与Fe-MOF共孵育后,协同激光照射处理,使用荧光显微镜观察其活性氧(Reactive Oxygen Specis, ROS)、脂质过氧化物(Lipid PerOxide, LPO)的生成以及细胞活/死染色情况;观察纳米探针在不同的pH条件下T1加权成像的激活效应,并在细胞水平测量不同时间点的T1激活效能。结果: 制备的Fe-MOF纳米探针呈针状结构,厚度约为44 nm;在体外溶液水平可有效促进ROS的生成及LPO的消耗;荧光显微镜结果显示Fe-MOF触发的铁死亡效应联合光动力治疗可有效促进细胞内ROS和LPO的生成及肿瘤细胞死亡;MR成像结果显示,在酸性条件下纳米探针的T1信号可被特异性激活,且具有较好pH响应性及细胞水平时间依赖性激活效能。结论:pH响应诊疗一体化的Fe-MOF纳米探针可实现乳腺癌的光动力增敏铁死亡效能以及MR微环境响应激活成像。
英文摘要:
      Objective: To synthesize tumor acidic microenvironment-responsive Fe-MOF nanoprobe and investigate its synergistic therapeutic effect of ferroptosis-photodynamic therapy for breast cancer and in vitro MR T1 activation effect. Methods: Fe-MOF nanoprobes were prepared and characterized by transmission electron microscope (TEM) and atomic force microscopy (AFM); Assess its reactive oxygen specis (ROS) generation capability and GSH depletion ability at the solution level using 3,3'',5,5''-Tetramethylbenzidine (TMB) and 5,5''-Dithiobis(2-nitrobenzoic acid) (DTNB); The MTT assay was used to determine the cytotoxicity of the nanoprobe on 4T1 breast cancer cells under dark and light conditions, so as to evaluate synergistic therapeutic effect of ferroptosis-photodynamic therapy; After the 4T1 cells were co-incubated with Fe-MOF and treated with laser irradiation, the generation of ROS, lipid peroxide (LPO) and cell live/dead staining were observed using the fluorescence microscope; Observe the activation effect of Fe-MOF in T1-weighted imaging under different pH conditions, and measure the T1 activation efficiency at different time points at the cellular level. Results: The prepared Fe-MOF nanoprobes exhibit a needle-like structure, with a thickness of approximately 44 nm; Fe-MOF can effectively promote the generation of ROS and the consumption of LPO at the solution level; Fluorescence microscope results show that ferroptosis effect triggered by Fe-MOF combined with photodynamic therapy can effectively promote the generation of intracellular ROS and LPO and tumor cell death; MR imaging results show that the T1 signal of Fe-MOF can be specifically activated under acidic conditions, and has good pH responsiveness at the solution level and time-dependent activation efficiency at the cellular level. Conclusions: The pH-responsive diagnostic and therapeutic integrated nanoprobe, Fe-MOF, is capable of achieving synergistic therapeutic efficacy through ferroptosis-photodynamic treatment and magnetic resonance T1 contrast effect.
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