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Dual-Targeting Upconversion Nanoprobes across the Blood–Brain Barrier for Magnetic Resonance/Fluorescence Imaging of Intracranial Glioblastoma

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† State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
‡ Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
§ Department of Radiology, Shanghai Cancer Hospital, Fudan University, Shanghai 200032, China
*Address correspondence to [email protected], [email protected]
Cite this: ACS Nano 2014, 8, 2, 1231–1242
Publication Date (Web):January 7, 2014
https://doi.org/10.1021/nn406197c
Copyright © 2014 American Chemical Society
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Abstract

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Surgical resection, one of the main clinical treatments of intracranial glioblastoma, bears the potential risk of incomplete excision due to the inherent infiltrative character of the glioblastoma. To maximize the accuracy of surgical resection, the magnetic resonance (MR) and fluorescence imaging are widely used for the tumor preoperative diagnosis and intraoperative positioning. However, present commercial MR contrast agents and fluorescent dyes can only function for single mode of imaging and are subject to poor blood–brain barrier (BBB) permeability and nontargeting-specificity, resulting in the apparent risks of inefficient diagnosis and resection of glioblastoma. Considering the unique MR/upconversion luminescence (UCL) bimodal imaging feature of upconversion nanoparticles (UCNPs), herein, we have developed a dual-targeting nanoprobe (ANG/PEG-UCNPs) to cross the BBB, target the glioblastoma, and then function as a simultaneous MR/NIR-to-NIR UCL bimodal imaging agent, which showed a much enhanced imaging performance in comparison with the clinically used single MRI contrast (Gd-DTPA) and fluorescent dye (5-ALA). Moreover, their biocompatibility, especially to brains, was systematically assessed by the histological/hematological examination, indicating a negligible in vivo toxicity. As a proof-of-concept, the ANG/PEG-UCNPs hold the great potential in MR diagnosis and fluorescence positioning of glioblastoma for the efficient tumor surgery.

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Synthetic procedures for UCNPs, OA-free UCNPs, PEG-UCNPs, ANG/PEG-UCNPs, and other supplementary figures. This material is available free of charge via the Internet at http://pubs.acs.org.

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