Protein misfolding and aggregation in the human organ and tissue system could lead to a series of serious neurodegenerative diseases, such as Alzheimer's [1], [2], Parkinson's disease [3] and type Ⅱ diabetes mellitus [4], [5]. The formed protein aggregates were named amyloid fibrils. It was well known that the formed amyloid fibrils were rich in β-sheet structure [6]. Until now, there was no effective therapy to cure these diseases. Retarding the formation of amyloid fibrils or destroying the formed amyloid fibrils were considered as effective methods for treatment of these protein diseases [7], [8], [9]. A large number of studies have been performed to synthesize or screen the inhibitor to prevent the formation of amyloid fibrils [10], [11]. Nowadays, many synthesized and natural extracted compounds have been studied to evaluate their influences on the procedure of amyloid fibrillation [12], [13].

Quantum dots, as a kind of nanomaterials, have received a lot of attention in recent years. It could be divided into inorganic and organic quantum dots. Inorganic quantum dots were usually utilized in semiconducting and optical fields [14], [15]. However, they were rarely used in biomedical field due to their cytotoxicity to the human body. Organic quantum dots were mainly composed of carbon elements, and they were also known as carbon quantum dots (CQDs) [16]. They were extensively utilized in biological, medical and biochemical fields because of their good biocompatibility and non-cytotoxicity to the human body [17], [18]. They were also reported as inhibitor on amyloid fibrillation of protein. Despite of these reports, the development of new CQDs-based inhibitor on amyloidosis still remained elusive and required further efforts.

Carbon quantum dots could be synthesized through top-down or bottom-up methods. In bottom-up methods, the precursor molecules firstly reacted to form polymer molecule and the polymer molecule was further carbonized under high temperature to obtain the carbon quantum dots [14], [19]. These kinds of carbon quantum dots could be named carbonized polymer dots (CPDs). The structure of precursor could be partly inherited to CPDs and the properties of the CPDs were closely related to the precursor molecules, which was important for the design of CPDs as inhibitors on protein amyloid aggregation.

Flavonoid compound, as a kind of natural substance, possessed many pharmacological activities, such as anti-oxidant, anti-inflammatory, anti-cancer properties [5], [9], [20]. It was also reported that many flavonoid compounds could intervene the protein amyloid aggregation [21], [22]. However, organic solvent must be added in the fibrillation experiment due to their poor water-solubility, which greatly limited their application as drugs in clinical medicine [23], [24]. The application of flavonoid compounds in medicine as drugs would be broadened if their water-solubility was increased.

The objective of this research was to obtain flavonoid-derived CPDs with good water-solubility through green synthesis method and the bioactivities of flavonoid compounds also could be retained in the CPDs. Four CPDs were prepared using four flavonoid compounds with different number of phenolic hydroxyl groups as precursors, respectively. Meanwhile, arginine was added to react with flavonoid compounds to improve the water-solubility of prepared CPDs. The prepared CPDs, as we expected, showed good water-solubility. The influences of four CPDs on protein amyloid aggregation were further investigated using hen egg white lysozyme (HEWL) and human lysozyme (HL) as model protein in aqueous solution. All of these four CPDs could intervene the formation of amyloid fibrils and the inhibition capability was greatly related to the number of phenolic hydroxyl groups. Luteolin-derived carbonized polymer dots (CPDs-1) showed the highest inhibition ratio compared with the other three CPDs under the same experimental conditions. The inhibition ratio of CPDs-1 on HEWL and HL reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 could retard amyloid aggregation of the protein and also could disaggregate the formed mature amyloid fibrils into short aggregates. This study could provide a new strategy for treatment of amyloid related disease and open new avenue for application of CPDs in medical fields.