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

Abstract

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.

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

“…Recently, several studies have used angiopep-2 as a dual targeting ligand to successfully deliver imaging probes to brain tumors. Ni et al modified angiopep-2 onto upconversion NPs that were loaded with gadolinium for magnetic resonance imaging (MRI) and fluorescence imaging (Ni et al 2014). Results showed this dual targeting system provided better contrast for brain imaging than the commercial MRI contrast (Gd-DTPA) and fluorescence probe (five-aminolevulinic acid).…”

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

“…The combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Various multimodal imaging schemes are designed for facile combination between NIRF probes and traditional imaging approaches that offer in vivo tumor images with excellent spatial resolution, such as MRI, 16,[83][84][85][86] CT, PETS, 87 single photon emission computed tomography (SPECT), 88 PAI, 89 Raman imaging, 90,91 etc. The main multimodal strategies are superparamagnetic iron oxide and gadolinium MR contrast conjugated with NIRF dyes or NPs.…”

Gadolinium‐Doped Iron Oxide Nanoprobe as Multifunctional Bioimaging Agent and Drug Delivery System

“…Over the past decade, many nanocarriers, including organic, inorganic, and hybrid ones, have been developed as targeted drug delivery systems for transporting therapeutic agents to disease sites. [ 7,27,28 ] The intrinsic instable nature of organic systems precludes on their clinical use. In contrast, IONs have clinical promise because of their capacity to simultaneously serve dual roles: as targeted vehicles for controlled release of drugs and as imaging probes for MRI.…”