Multifunctional upconversion nanoparticles for targeted dual-modal imaging in rat glioma xenograft

Purpose: Achieving a radiographic gross total resection in high-grade gliomas improves overall survival. Many technologies such as intraoperative microscope, intraoperative ultrasound, fluorescence imaging, and intraoperative magnetic resonance imaging have been applied to improve tumor resection. However, most commercial available magnetic resonance imaging contrast agents have limited permeability across the blood-brain barrier and are cleared rapidly from circulation. Fluorescence imaging discriminates tumor from normal tissue and provides a promising new strategy to maximize sage surgical resection of tumor. However, the penetration depth of fluorescence imaging is generally low.

Materials and methods: In this study, a new type of magnetite NaGdF4:Yb(3+),Er(3+),Li(+)@NaGdF4 (UCNPs) core-shell nanoparticles, coated with SiO2 and further functionalized with glioma and blood-brain barrier targeting motifs, was prepared for dual-modal in vivo upconversion imaging and magnetic resonance imaging.

Results: The as-prepared multifunctional upconversion nanoparticles (UCNPs@SiO2-CX-Lf) were biocompatible, showed strong upconversion luminescence under excitation of 980 nm, and provided high signal-to-noise ratio in vivo. Moreover, UCNPs@SiO2-CX-Lf nanoparticles showed a high relaxivity of 1.25 S(-1 )mM(-1) and were successfully applied as contrast agent for magnetic resonance imaging in tumor xenograft rat model with prolonged tumor signal enhancement. In vivo and magnetic resonance imaging Upconversion Luminescence (UCL) imaging results indicated that these particles can across the blood-brain barrier, bind to glioma, gave bright UCL signal and T1 magnetic resonance imaging contrast.

Conclusions: Targeted UCL and magnetic resonance imaging dual-modal in vivo imaging using Yb(3+)/Er(3+)/Li(+) codoped NaGdF4 core-shell nanostructure can serve as a platform technology for the next generation of intraoperative probes for image-guided tumor resection.