title: A multimodal Pepstatin A peptide-based nanoagent for the molecular imaging of P-glycoprotein in the brains of epilepsy rats.
abstract: Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissues may lower antiepileptic drugs concentrations at the target site and contribute to pharmacoresistance in refractory epilepsy. However, few techniques are available to quantitate the level of P-gp expression noninvasively in vivo. In this study, we developed a nanoagent by conjugating superparamagnetic iron oxide nanoparticles with a near infrared probe and the targeting element Pepstatin A, a peptide with specific affinity for P-gp. In a rat model of epilepsy, the nanoagent was readily and selectively accumulated within epileptogenic cerebral regions, which were detectable by both magnetic resonance imaging and optical imaging modalities. This P-gp-targeted nanoagent could be used not only in the molecular imaging of P-gp expression changes in seizure-induced regional, understanding the mechanisms of P-gp disorders, and the prediction of refractory epilepsy, but also in targeted therapies with P-gp modulators.
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Shen
authors.affiliation: Instrumental Analysis Center, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Zhonglian
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: zqpang@fudan.edu.cn.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China. Electronic address: daoyinggeng@163.com.
authors.forename: Daoying
authors.initials: D
authors.lastname: Geng
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China. Electronic address: zj810828@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004827:Epilepsy / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D036103:Nanotechnology; D010436:Pepstatins / Q000008:administration & dosage*; D051381:Rats
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D010436:Pepstatins; C031375:pepstatin
keywords: Epilepsy; Magnetic resonance imaging; Multimodal nanoagent; Optical imaging; P-glycoprotein