Passage of Magnetic Tat-Conjugated Fe3O4@SiO2 Nanoparticles Across In Vitro Blood-Brain Barrier.

Xueqin Zhao,Xiaodan Zhang,Ting Ye,Lei Rei,Dajin Wang,Ting Shang

doi:10.1186/s11671-016-1676-2

Xueqin Zhao, Xiaodan Zhang + Show 4 more

Open Access

https://doi.org/10.1186/s11671-016-1676-2

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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@Fe3O4 nanoparticle-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.

Highlights

The blood-brain barrier (BBB) comprised of brain capillary endothelial cells is the most restrictive barrier in vivo that hampers the transport of s ubstances from the peripheral circulation to the brain and helps maintain brain homeostasis [1]
A number of cell-penetrating peptides (CPPs) including trans-activating transcriptional activator (TAT), angiopep, penetratin, rabies virus glycoprotein (RVG), prion peptide, and SynB have already been demonstrated the ability of improving drug delivery across the BBB [23, 24]
In vitro BBB model may keep the status of BBB integrity, which helps to be understood in terms of how BBB facilitate or interfere with drug delivery [28]

Summary

Introduction

The blood-brain barrier (BBB) comprised of brain capillary endothelial cells is the most restrictive barrier in vivo that hampers the transport of s ubstances from the peripheral circulation to the brain and helps maintain brain homeostasis [1]. Different strategies for bypassing the BBB have been developed, including direct injection into the brain, transient disruption of the BBB, inhibition of efflux pumps, pro-drug strategy, and receptor-mediated transcytosis [4,5,6,7,8]. A number of CPPs including trans-activating transcriptional activator (TAT), angiopep, penetratin, rabies virus glycoprotein (RVG), prion peptide, and SynB have already been demonstrated the ability of improving drug delivery across the BBB [23, 24]. It has been demonstrated that Tat-conjugated nanoparticles can deliver siRNA and drug across the BBB to kill intracerebral malignant glioma cells and further extend the mouse life span [26]. In vitro BBB model may keep the status of BBB integrity, which helps to be understood in terms of how BBB facilitate or interfere with drug delivery [28]

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