A multi-target theranostic nano-composite against Alzheimer's disease fabricated by conjugating carbon dots and triple-functionalized human serum albumin

Abstract

The complex pathogenesis of Alzheimer's disease (AD) involves the aggregation and accumulation of amyloid β-protein (Aβ) as well as elevated levels of reactive oxygen species (ROS), which requires the development of comprehensive diagnostic and therapeutic interventions. In this work, a multifunctional theranostic nano-composite (HSA-BFP@CDs) is constructed by conjugating triple-functionalized human serum albumin (HSA-BFP) as a theranostic agent targeting Aβ and carbon dots (CDs) as an ROS scavenger. HSA-BFP@CDs exhibits a fluorescence “off-on” effect at 700 nm upon interaction with Aβ aggregates, showing the capability for detection of Aβ plaques and potential for early diagnosis of AD. Besides, HSA-BFP@CDs effectively inhibits the aggregation of Aβ, increasing the viability of Aβ-treated cells from 74% to over 95% at 100 µg/mL. Moreover, multiple ROS, including hydroxyl radicals, superoxide radicals, hydrogen peroxide, and Aβ-Cu2+-induced-ROS, can be scavenged by HSA-BFP@CDs, thus resulting in the mitigation of cellular oxidative damages. Experiments with the AD model of Caenorhabditis elegans further demonstrate the multifunctionality of HSA-BFP@CDs in imaging amyloid plaques, reducing Aβ deposition, and relieving oxidative stress in vivo, showing the prospect for Aβ- and ROS-targeted AD diagnosis and treatment. This work provided new insight into the design of protein-carbon dots conjugate and the development of multi-target therapy of AD. Statement of significanceAlzheimer's disease (AD) is the most common form of dementia, which currently affects over 55 million people worldwide. Due to the complex pathogenesis of AD involving amyloid β-protein (Aβ) aggregation as well as elevated levels of reactive oxygen species (ROS), it is highly desired to develop comprehensive diagnostic and therapeutic interventions. In this paper, we fabricated a multifunctional theranostic nano-composite (HSA-BFP@CDs) via the conjugation of triple-functionalized human serum albumin (HSA-BFP) and carbon dots (CDs). The multifunctionality of HSA-BFP@CDs for efficient detection of Aβ aggregates and inhibition of Aβ aggregation as well as scavenging of ROS was demonstrated, demonstrating the potential of the protein-carbon dots conjugate for the multi-target therapy of AD.