Chiral carbon dots: a smart choice for inhibition of human serum albumin fibrillation

Abstract

Human serum albumin (HSA) is a crucial protein in the human body, serving as a carrier for various small molecules and playing a vital role in maintaining osmotic pressure in the bloodstream. However, misfolding and fibrillation of HSA can lead to a range of pathological conditions, including amyloidosis. In recent years, researchers have explored several innovative strategies to inhibit HSA fibrillation, and one of the promising avenues is the utilization of chiral compounds that can offer an effective means of modulating the 'structural integrity of the protein. Among the most prevalent chiral compounds, chiral carbon dots (CCDs) are renowned for their distinctive physicochemical properties, offering unique stereochemical properties, assuming a pivotal role in attaining circularly polarized luminescence that can be harnessed for inhibiting HSA fibrillation. Recent advancement of carbon-based chiral nanostructures has attracted widespread attention in the field of nanobiotechnology owing to their overwhelming chemical, optical and electronic properties. However, being an emerging type of chiral nanomaterial, chiral CDs (CCDs) are still at their primary research stage. Herein, we have developed a simple methodology to quickly synthesize chiral carbon dots (L/D-TA-C-dots) of size ranging from 3 to 7 nm by microwave-assisted pyrolysis of L/D-tartaric acid, respectively. The circular dichroism spectrum of L/D-TA-C-dots has demonstrated characteristic peaks with opposite nature at around 230–232 nm corresponding to the n → π* transition of CO groups. The synthesized L/D-C-dots have exhibited stable and intense luminescence at 460 nm. A variety of biophysical techniques such as thioflavin-T fluorescence, circular dichroism, fluorescence microscopy, transmission electron microscopy and atomic force microscopy have suggested that the L-TA-C-dots are more effective in hindering the fibrillation process of HSA than D-TA-C-dots. Further, the potential of the synthesized L-TA-C-dots to inhibit the formation of human serum albumin (HSA) fibrils has been investigated in vitro. The biocompatibility of water-soluble L-TA-C-dots has been confirmed by determining the cellular uptake efficiency through a localization study after exposing them to MDA-MB-231 cells. Besides, the thermodynamic parameters for the interaction of HSA monomers with L/D-TA-C-dots have also been calculated, which suggests that the preferential hydrophobic interaction between HSA monomers and L-C-dots restricts the self-assembly of HSA at an early stage, leading to inhibition of fibrillation. The promising results of chiral L-TA-C-dots provide an opportunity to exploit them in the field of in vivo bioimaging and can be used as promising therapeutic agents for various amyloidogenic disorders.