Sensitive imaging and effective capture of Cu(2+): Towards highly efficient theranostics of Alzheimer's disease

Abstract

As a distinct feature of Alzheimer's disease (AD), the presence of excess metal ions in the brain is most probably one of the main causative factors for the aggregation of β-Amyloid (Aβ) proteins. The design of nanoprobes for detection and control of ion concentrations will be of great importance in predicting the progression of AD and simultaneously providing effective treatments. Herein, we report the design and synthesis of a novel yet smart nanoprobe that can sensitively detect the Cu(2+) concentration and concurrently capture Cu(2+) both in vitro and in vivo. The designed nanoprobe (UCHQ) combines two main components: upconversion nanoparticles (UCNPs) used for the detection and upconversion luminescence (UCL) imaging of Cu(2+) upon 980 nm exposure and the chelator 8-hydroxyquinoline-2-carboxylic acid (HQC) used for chelating Cu(2+) and AD therapy. The results show that the emission intensity of UCHQ is highly dependent on the Cu(2+) concentrations due to the luminescence resonance energy transfer (LRET) from UCNPs to HQC-bonded Cu(2+). Fascinatingly, the as-constructed UCHQs could be used for UCL imaging of Aβ both in cells and AD mice. Most importantly, UCHQs could not only inhibit the Aβ aggregation-induced apoptosis via capturing overmuch Cu(2+) but also accelerate the nontoxic structural transformation of Aβ.

Keywords: Alzheimer's disease; LRET; Nanotheranostics; Sensing; Upconversion nanoparticles.