title: Casp3/7-Instructed Intracellular Aggregation of Fe3O4 Nanoparticles Enhances T2 MR Imaging of Tumor Apoptosis.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Zhanling
authors.initials: Z
authors.lastname: Ding
authors.affiliation: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences , 350 Shushanhu Road, Hefei, Anhui 230031, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Qian
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences , 350 Shushanhu Road, Hefei, Anhui 230031, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: School of Life Sciences, University of Science and Technology of China , Hefei, Anhui 230027, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Ge
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Luo
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences , 350 Shushanhu Road, Hefei, Anhui 230031, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhong
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China , 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Gaolin
authors.initials: G
authors.lastname: Liang
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology
chemical_list: D058185:Magnetite Nanoparticles; D009363:Neoplasm Proteins; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
keywords: Caspase 3/7; aggregation; magnetic resonance imaging; transverse relaxation; ultrasmall superparamagnetic iron oxide