Dual-targeting and excretable ultrasmall SPIONs for T1-weighted positive MR imaging of intracranial glioblastoma cells by targeting the lipoprotein receptor-related protein. Issue 11 (26th February 2020)

• Record Type: Journal Article
• Authors: Du, Chengjuan; Liu, Xianping; Hu, Hui; Li, Huiming; Yu, Luodan; Geng, Daoying; Chen, Yu; Zhang, Jun
• Is Part Of: Journal of materials chemistry. Volume 8:Issue 11(2020)
• Page Start: 2296
• Page End: 2306
• Publication Date: 2020-02-26
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c9tb02391g
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : A multifunctional targeted nanoprobe composed of ultrasmall superparamagnetic iron oxide nanoparticles with surface-conjugated Angiopep-2 was successfully constructed for targeted MR imaging of intracranial glioblastoma. Abstract : A precise delineation of the intracranial glioblastoma boundary is urgently required for pre-surgical operations, due to the tumor-inherent infiltrative character of a tumor and the difficulty to completely remove the tumor. Magnetic resonance (MR) imaging is the leading clinical diagnostic tool for brain tumors, where a safe MR contrast agent that targets cancer biomarkers is critical for non-invasive 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 constructed by a stepwise reaction. The nanoprobe efficiently crossed the blood–brain barrier (BBB), targeted the glioblastoma and then generated positive contrast enhancement for T 1 -weighted MR imaging. Angiopep-2 was herein selected as a targeting ligand to construct the dual-targeting nanoprobes for MR imaging of brain tumors, because it can specifically combine to the low-density lipoprotein receptor-related protein (LRP), which is overexpressed in both BBB and glioblastoma cells. The targeting capability and, in particular, the biocompatibility/excretion of these ANG-modified MRI nanoprobes were systematically evaluated not only at the intracellular level in vitro, but also on tumor xenografts in vivo . This first report on ANG-engineered USPIONs as T 1 -weighted positive MR contrast agents for intracranial targeted glioblastoma imaging, provides a promising application potential for these SPION-based ultrasmall nanoprobes, not only for efficient pre-operative tumor diagnosis, but also for the targeted surgical resection of intracranial glioblastomas.