Design of Multifunctional Agent Based on Basified Serum Albumin for Efficient In Vivo β-Amyloid Inhibition and Imaging.

Theranostics, the combination of therapeutics and diagnostics, has emerged as a sophisticated, integrated, and advanced tool in the prevention and treatment of serious diseases, such as Alzheimer's disease (AD). However, the preclinical research of an AD theranostic molecule is in its infancy and needs to be explored in depth. Herein, a multifunctional theranostic agent is designed and fabricated by conjugating an Aβ-specific near-infrared (NIR) fluorescence probe ( F ) and by coupling a BBB penetrable peptide (Penetratin, Pen) onto the basified human serum albumin (HSA-B) that has been recently proven as an effective amyloid-β (Aβ) inhibitor. Such an elaborately constructed HSA-B-based molecule (HSA-BFP) possesses high potency on inhibiting Aβ fibrillogenesis, for example, increasing SH-SY5Y cell viability from 66.5 to 93%. In addition, HSA-BFP exhibits favorable stability in the "off-on" NIR imaging of Aβ plaques and achieves a 2-fold increase of BBB permeability after the Pen modification. More importantly,  in vivo assays with the AD model C. elegans CL2006 indicate that HSA-BFP can specifically image Aβ deposits, decrease amyloid accumulation, and attenuate Aβ-triggered paralysis. Thus, HSA-B has been proven as a potent and versatile platform for the development of AD theranostic agents.