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 T1-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 T1-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.
March 8, 2021
Zika virus infection during pregnancy protects against secondary infection in the absence of CD8 cells.
April 19, 2021
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