# Liraglutide-Conjugated Poly(methyl vinyl ether-alt-maleic acid)-Coated Core–Shell Upconversion Nanoparticles for Theranostics of Diabetes

## TL;DR

This paper introduces a new type of nanoparticle that can target and image insulin-deficient beta cells in the pancreas, potentially improving diabetes diagnostics and treatment.

## Contribution

The novel contribution is the development of liraglutide-conjugated upconversion nanoparticles with enhanced targeting and imaging capabilities for pancreatic beta cells.

## Key findings

- CS-UCNP@PMVEMA-LGL nanoparticles showed increased glucose-stimulated insulin secretion from pancreatic islets.
- In vivo imaging demonstrated enhanced nanoparticle accumulation in the pancreas after intramuscular injection.
- Confocal microscopy confirmed receptor-mediated uptake of nanoparticles by pancreatic beta cells.

## Abstract

In the diagnostics of diabetes, specific targeting of
drugs (e.g.,
liraglutide) to insulin-deficient β-cells with their simultaneous
noninvasive imaging is currently needed. In this report, liraglutide
(LGL)-conjugated poly­(methyl vinyl ether-alt-maleic
acid) (PMVEMA)-coated core–shell NaYF4:Yb,Er,Fe@NaYF4:Nd upconversion nanoparticles (CS-UCNPs) have been developed,
thoroughly physicochemically characterized, and evaluated in vivo. Novel codoping of Fe2+, Yb3+, and Er3+ ions in the host NaYF4 induced upconversion
emission in the red region at both 980 and 808 nm excitation, making
the particles suitable for deep-tissue imaging. Surface functionalization
with PMVEMA provided colloidal stability and facilitated covalent
conjugation with LGL, enabling targeted binding to GLP-1 receptors
on pancreatic β-cells, increasing glucose-stimulated insulin
secretion from isolated Langerhans islets. Biocompatibility of CS-UCNP@PMVEMA-LGL
nanoparticles was confirmed by the trypan blue dye exclusion assay.
When the fluorescent dye Flamma was conjugated to the nanoparticles, in vivo fluorescence imaging revealed significantly enhanced
accumulation of CS-UCNP@PMVEMA-LGL-Flamma nanoparticles in the pancreas
24 h after intramuscular injection compared with intravenous administration,
with luminescence intensity approximately doubled. The improved pancreatic
targeting efficiency was attributed to enhanced binding to GLP-1 receptors.
Confocal microscopy and elemental analysis confirmed receptor-mediated
uptake of the nanoparticles by internalization and their localization
within pancreatic β-cells. These findings highlight the potential
of CS-UCNP@PMVEMA-LGL nanoparticles as biocompatible targetable imaging
agents with future applications in pancreatic diagnostics.