title: Passage of Magnetic Tat-Conjugated Fe3O4@SiO2Nanoparticles Across In Vitro Blood-Brain Barrier.
abstract: Delivery of diagnostic or therapeutic agents across the blood-brain barrier (BBB) remains a major challenge of brain disease treatment. Magnetic nanoparticles are actively being developed as drug carriers due to magnetic targeting and subsequently reduced off-target effects. In this paper, we developed a magnetic SiO2@Fe3O4nanoparticle-based carrier bound to cell-penetrating peptide Tat (SiO2@Fe3O4﻿-Tat﻿) and studied its fates in accessing BBB. SiO2@Fe3O4-Tat nanoparticles (NPs) exhibited suitable magnetism and good biocompatibility. NPs adding to the apical chamber of in vitro BBB model were found in the U251 glioma cells co-cultured at the bottom of the Transwell, indicating that particles passed through the barrier and taken up by glioma cells. Moreover, the synergistic effects of Tat and magnetic field could promote the efficient cellular internalization and the permeability across the barrier. Besides, functionalization with Tat peptide allowed particles to locate into the nucleus of U251 cells than the non-conjugated NPs. These results suggest that SiO2@Fe3O4-Tat NPs could penetrate the BBB through the transcytosis of brain endothelial cells and magnetically mediated dragging. Therefore, SiO2@Fe3O4-Tat NPs could be exploited as a potential drug delivery system for chemotherapy and gene therapy of brain disease.
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China. zhaoxueqin2004@163.com.
authors.forename: Xueqin
authors.identifier: http://orcid.org/0000-0002-4214-6599
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Shang
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
authors.forename: Dajin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, People's Republic of China. renlei@xmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Rei
keywords: Blood-brain barrier; Magnetic nanoparticles; Magnetic targeting; Tat peptide; hCMEC/D3 cell