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

The incomplete detection of glioblastomaor the remnantsof surgeryconstitute 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 misseddiagnosis or inaccurate boundary identification. MR contrast agentshave been widely explored in conjugation with tumor-specific markersto preoperatively diagnose and identify the intraoperative positioningof glioblastoma. Herein, we developed a type of upconversion nanoparticle(UCNP), KMnF3:18%Yb, 2%Er, via the typical hydrothermalmethod, which possesses unique MR upconversion luminescence bimodalimaging. Furthermore, UCNPs were transformed to the aqueous phaseby replacing oleic acid with amine-polyethylene glycol (PEG)-thiol(NH2-PEG-SH), further enabling the covalentconjugation of the glioblastoma metabolic ligand biotin. The as-preparedmultifunctional biotin/PEG-UCNPs were characterized using varioustechniques. Moreover, their biocompatibility, especially with thebrain, was systematically assessed via histological and hematologicalexaminations. The results indicated negligible toxicity invivo. As a proof of concept, biotin/PEG-UCNPs exhibitedconsiderable potential for accurate definition of glioma infiltrationboundaries for surgery as metabolic dual imaging contrast agents.