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

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 SIGNIFICANCE: Alzheimer'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.