Casp3/7-Instructed Intracellular Aggregation of Fe3O4 Nanoparticles Enhances T2 MR Imaging of Tumor Apoptosis

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• 作者：Yue Yuan ; Zhanling Ding ; Junchao Qian ; Jia Zhang ; Jinyong Xu ; Xuejiao Dong ; Tao Han ; Shuchao Ge ; Yufeng Luo ; Yuwei Wang ; Kai Zhong ; Gaolin Liang
• 刊名：Nano Letters
• 出版年：2016
• 出版时间：April 13, 2016
• 年：2016
• 卷：16
• 期：4
• 页码：2686-2691
• 全文大小：418K
• 年卷期：0
• ISSN：1530-6992

文摘

Large magnetic nanoparticles or aggregates are advantageous in their magnetic resonance properties over ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs), but the former are cleared faster from the blood pool. Therefore, the “smart” strategy of intracellular aggregation of USPIO NPs is required for enhanced T₂-weighted MR imaging. Herein, employing an enzyme-instructed condensation reaction, we rationally designed a small molecule Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys-CBT (1) to covalently modify USPIO NPs to prepare monodispersive Fe₃O₄@1 NPs. In vitro results showed that Fe₃O₄@1 NPs could be subjected to caspase 3 (Casp3)-instructed aggregation. T₂ phantom MR imaging showed that the transverse molar relaxivity (r₂) of Fe₃O₄@1 NPs with Casp3 or apoptotic HepG2 cells was significantly larger than those of control groups. In vivo tumor MR imaging results indicated that Fe₃O₄@1 NPs could be specifically applied for enhanced T₂ MR imaging of tumor apoptosis. We propose that the enzyme-instructed intracellular aggregation of Fe₃O₄ NPs could be a novel strategy for the design of “smart” probes for efficient T₂ MR imaging of in vivo biomarkers.