A multifunctional theranostic agent based on rhodamine-modified copper-gallic acid nanoparticles targeting Alzheimer’s β‑amyloid species
Luqi Liu, Wei Liu, Xiaoyan Dong, Yan Sun
Abstract
β-Amyloid protein (Aβ) fibrillogenesis accompanied by the accumulation of reactive oxygen species (ROS) and neuroinflammation is an imperative cascade event during Alzheimer’s disease (AD) progression. However, effective diagnosis and therapy for AD remain a major challenge due to low detection sensitivity, weak Aβ inhibitory potency, and lack of multi-target intervention modality. To address these, a multifunctional theranostic agent that targets Aβ species is proposed by coordinating copper-gallic acid nanoparticles (Cu-GA NPs) with rhodamine derivative (Rho4). Such elaborately constructed Rho4-modified nanoparticles (Rho4@Cu-GA NPs) show excellent fluorescent detection capabilities toward Aβ species, with a detection limit of 59 nM toward Aβ oligomers. Rho4@Cu-GA NPs effectively inhibit Aβ fibrillogenesis via multivalent interactions and alleviate Aβ-induced cytotoxicity and apoptosis. Meanwhile, Rho4@Cu-GA NPs exhibit superior ROS scavenging capabilities, thus mitigating neuronal oxidative stress triggered by Aβ and ROS and downregulating neuroinflammatory cytokines secreted by microglial cells. In vivo assays with transgenic AD mice demonstrate that Rho4@Cu-GA NPs can penetrate the blood–brain barrier, illuminate Aβ deposits, reduce Aβ plaque deposition, and improve cognition deficits. Therefore, this protocol triggered the combination of early diagnosis and multi-target therapy of AD, which would give deep insight into the development of potent AD theranostic agents.