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Dual-targeting and Execrable Ultrasmall SPIONs for T1-weighted Positive MR Imaging of Intracranial Glioblastoma by Targeting Lipoprotein Receptor-Related Protein

Abstract

A precise delineation of intracranial glioblastoma boundary is urgently in need for pre-surgical operation because of the tumor inherent tumor infiltrative character and the difficulty to completely remove tumor. Magnetic resonance (MR) imaging is the leading clinical diagnostic modality of brain tumors, where a safe MR contrast agent targeting cancer biomarkers is critical for noninvasive and accurate brain-tumor detection. In this work, a multifunctional targeted nanoprobe composed of PEGylated ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), with surface conjugated Angiopep-2 was successfully stepwise constructed, which efficiently crossed the blood-brain barrier (BBB), targeted the glioblastoma and then generated positive contrast enhancement for T1-weighted MR imaging. Angiopep-2 was herein selected as a targeting ligand to construct the dual-targeting nanoprobes for MR imaging of brain tumor, because it could specifically combine to the low-density lipoprotein receptor related protein (LRP), which overexpressed on both BBB and glioblastoma cells. The targeting capability and especially the biocompatibility/excretion of these ANG-modified MRI nanoprobes were systematically evaluated not only at intracellular level in vitro but also on tumor xenografts in vivo. This first report on ANG-engineered USPIONs as T1-weighted positive MR contrast agent for intracranial targeted glioblastoma imaging, provides a promising application potential of these SPIONs-based ultrasmall nanoprobes not only for efficient pre-operative tumor diagnosis, but also for targeted surgical resection of intracranial glioblastoma.

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Supplementary files

Article information


Submitted
29 Oct 2019
Accepted
31 Jan 2020
First published
02 Feb 2020

J. Mater. Chem. B, 2020, Accepted Manuscript
Article type
Paper

Dual-targeting and Execrable Ultrasmall SPIONs for T1-weighted Positive MR Imaging of Intracranial Glioblastoma by Targeting Lipoprotein Receptor-Related Protein

C. Du, X. Liu, H. Hu, H. Li, L. Yu, D. Geng, Y. Chen and J. Zhang, J. Mater. Chem. B, 2020, Accepted Manuscript , DOI: 10.1039/C9TB02391G

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