Multimodal Nanoprobe for Pancreatic Beta Cell Detection and Amyloidosis Mitigation

Abstract

Type 2 diabetes (T2D) is a metabolic disease and a global health crisis. Because of the small mass and high dispersity of beta cells in the pancreas, especially among T2D patients, it remains a tremendous challenge to detect and image beta cell mass (BCM) in vitro and in vivo. Herein, a multimodal nanoprobe is constructed by surface functionalization of magnetic iron oxide nanoparticles with a two-photon fluorescent dye (NaP)-labeled polymer. Owing to the nanoparticle surface energy-transfer effect, the nanoprobe enabled pH-triggered fluorescence/magnetic resonance imaging in the acidic beta cell environment. Specifically, confocal one-photon and two-photon modalities revealed prominent fluorescence in BTC-6 pancreatic beta cells among five major cell types, validating the probe as a sensor for BCM quantification. Kinetic assay, transmission electron microscopy, and viability assay further implicated the probe as a potent inhibitor against the aggregation and toxicity of human islet amyloid polypeptide (IAPP), the peptide associated with T2D. This probe presents a first multimodal theranostic system for imaging BCM and inhibition of beta cell degeneration by IAPP amyloidosis.