Upconverting Nanoparticles for Bimodal Luminescence and Magnetic Resonance Imaging of Langerhans Islets

Combining luminescence with magnetic resonance imaging (MRI) is a noninvasive approach that significantly improves detection sensitivity and diagnostic precision for severe diseases. In diabetes care, this approach considerably broadens the possibilities for monitoring of Langerhans islet transplantation by improving their detectability and quantification within existing imaging modalities, including MRI. To realize this concept, upconverting nanoparticles (UCNPs) appear particularly promising, providing bimodal MRI and luminescence with the ability of near-infrared (NIR) light to penetrate deep into tissues. In this work, novel monodisperse dumbbell-shaped core-shell UCNPs (CS-UCNPs) coated with poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) are developed for the bimodal imaging of Langerhans islets. Codoping of Fe, Yb, and Er ions in the NaYF₄ host matrix, along with the presence of NaGdF₄:Nd, Yb, Tb shell, increases both r ₁ and r ₂ relaxivities and upconversion luminescence in the red region, which is suitable for in vivo applications. The biocompatible PMVEMA coating ensures colloidal stability of the particles in aqueous physiological fluids and their nontoxicity. The potential of CS-UCNPs for simultaneous MRI and optical visualization is tested on isolated Langerhans islets. The efficiency of in vivo visualization of CS-UCNP@PMVEMA-labeled Langerhans islets transplanted under the kidney capsule in a rat model is investigated using T ₁-, T ₂-, and T ₂*-weighted MRI sequences.