Biotin-Conjugated Upconversion KMnF3/Yb/Er Nanoparticles for Metabolic Magnetic Resonance Imaging of the Invasive Margin of Glioblastoma

Abstract

The incomplete detection of glioblastoma or the remnants of surgery constitute the primary reasons underlying glioblastoma recurrence. However, the current commercial MR Gd-based contrast agents (GBCAs) are not specialized, thus posing a potentially high risk of missed diagnosis or inaccurate boundary identification. MR contrast agents have been widely explored in conjugation with tumor-specific markers to preoperatively diagnose and identify the intraoperative positioning of glioblastoma. Herein, we developed a type of upconversion nanoparticle (UCNP), KMnF3:18%Yb, 2%Er, via the typical hydrothermal method, which possesses unique MR upconversion luminescence bimodal imaging. Furthermore, UCNPs were transformed to the aqueous phase by replacing oleic acid with amine–polyethylene glycol (PEG)–thiol (NH2–PEG–SH), further enabling the covalent conjugation of the glioblastoma metabolic ligand biotin. The as-prepared multifunctional biotin/PEG–UCNPs were characterized using various techniques. Moreover, their biocompatibility, especially with the brain, was systematically assessed via histological and hematological examinations. The results indicated negligible toxicity in vivo. As a proof of concept, biotin/PEG–UCNPs exhibited considerable potential for accurate definition of glioma infiltration boundaries for surgery as metabolic dual imaging contrast agents.