pH-Responsive, Self-Sacrificial Nanotheranostic Agent for Potential In Vivo and In Vitro Dual Modal MRI/CT Imaging, Real-Time, and In Situ Monitoring of Cancer Therapy
pH-Responsive, Self-Sacrificial Nanotheranostic Agent for Potential In Vivo and In Vitro Dual Modal MRI/CT Imaging, Real-Time, and In Situ Monitoring of Cancer Therapy
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pH 响应型、自我牺牲型纳米治疗剂，可用于体内和体外双模式 MRI/CT 成像、实时和原位癌症治疗监测
DOI：
10.1021/acs.bioconjchem.6b00562
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发表时间：
2017
影响因子：
4.7
通讯作者：
Yu Dexin
中科院分区：
文献类型：
--
作者：
Yue Ludan;Wang Jinlong;Dai Zhichao;Hu Zunfu;Chen Xue;Qi Yafei;Zheng Xiuwen;Yu Dexin
多功能纳米治疗剂由于在图像引导癌症治疗中的应用而受到高度赞扬。在此，基于化学无序面心立方（fcc）FePt纳米颗粒（NP）和氧化石墨烯（GO），我们开发了一种pH响应性FePt基多功能治疗诊断剂，用于潜在的体内和体外双模态MRI/CT成像和原位癌症抑制。由于肿瘤细胞内pH值较低，fcc-FePt会释放出高活性的Fe离子，催化H2O2在细胞内分解为活性氧（ROS），进一步诱导癌细胞凋亡。与叶酸（FA）结合后，铁铂-二巯基丁二酸/聚乙二醇化氧化石墨烯-叶酸（FePt-DMSA/GO-PEG-FA）复合纳米组件（FePt/GO CNs）可以有效靶向FA受体阳性肿瘤细胞并表现出显着毒性，但对FA受体阴性正常细胞没有明显毒性，通过WST-1试验进行评估。基于 FePt 的多功能纳米粒子可以通过 T2 加权 MRI 实时监测 Fe 的释放，并且可以在注射后在体内估计 CT 中的选择性对比增强。结果表明，FePt基纳米粒子在体内外表现出优异的生物相容性和良好的MRI/CT成像能力。同时，FePt的分解会显着降低T2加权MRI信号并增加ROS信号，从而能够实时、原位可视化监测肿瘤细胞中Fe的释放。此外，fcc-FePt的自牺牲分解将有利于所制备的FePt基纳米复合材料在体内的自清除。因此，FePt/GO CNs可以作为MRI/CT成像指导临床癌症诊断和治疗的潜在多功能治疗诊断纳米平台。
Multifunctional nanotheranostic agents have been highly commended due to the application to image-guided cancer therapy. Herein, based on the chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) and graphene oxide (GO), we develop a pH-responsive FePt-based multifunctional theranostic agent for potential in vivo and in vitro dual modal MRI/CT imaging and in situ cancer inhibition. The fcc-FePt will release highly active Fe ions due to the low pH in tumor cells, which would catalyze H2O2decomposition into reactive oxygen species (ROS) within the cells and further induce cancer cell apoptosis. Conjugated with folic acid (FA), the iron platinum-dimercaptosuccinnic acid/PEGylated graphene oxide-folic acid (FePt-DMSA/GO-PEG-FA) composite nanoassemblies (FePt/GO CNs) could effectively target and show significant toxicity to FA receptor-positive tumor cells, but no obvious toxicity to FA receptor-negative normal cells, which was evaluated by WST-1 assay. The FePt-based multifunctional nanoparticles allow real-time monitoring of Fe release by T2-weighted MRI, and the selective contrast enhancement in CT could be estimated in vivo after injection. The results showed that FePt-based NPs displayed excellent biocompatibility and favorable MRI/CT imaging ability in vivo and in vitro. Meanwhile, the decomposition of FePt will dramatically decrease the T2-weighted MRI signal and increase the ROS signal, which enables real-time and in situ visualized monitoring of Fe release in tumor cells. In addition, the self-sacrificial decomposition of fcc-FePt will be propitious to the self-clearance of the as-prepared FePt-based nanocomposite in vivo. Therefore, the FePt/GO CNs could serve as a potential multifunctional theranostic nanoplatform of MRI/CT imaging guided cancer diagnosis and therapy in the clinic.