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

Autor: Junchao Qian, Kai Zhong, Jia Zhang, Jinyong Xu, Tao Han, Shuchao Ge, Yuwei Wang, Yufeng Luo, Yue Yuan, Gaolin Liang, Xuejiao Dong, Zhanling Ding
Rok vydání: 2016
Předmět:
Zdroj: Nano Letters. 16:2686-2691
ISSN: 1530-6992
1530-6984
Popis: 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.
Databáze: OpenAIRE