Multimodal Nanoprobe for Pancreatic Beta Cell Detection and Amyloidosis Mitigation
Fangyun Xin, Yuhuan Li, Changkui Fu, Ibrahim Javed, Xumin Huang, Anaïs Schaschkow, Rita Sofia Garcia Ribeiro, Esteban N. Gurzov, Thomas P. Davis, Xiaoling Zhang, Pu Chun Ke, Ruirui Qiao
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.