Dopamine-Conjugated Carbon Dots Inhibit Human Calcitonin Fibrillation

Abstract

The development of biocompatible nanomaterials has become a new trend in the treatment and prevention of human amyloidosis. Human calcitonin (hCT), a hormone peptide secreted from parafollicular cells, plays a major role in calcium–phosphorus metabolism. Moreover, it can be used in the treatment of osteoporosis and Paget’s disease. Unfortunately, it tends to form amyloid fibrils irreversibly in an aqueous solution, resulting in a reduction of its bioavailability and therapeutic activity. Salmon calcitonin is the replacement of hCT as a widely therapeutic agent due to its lower propensity in aggregation and better bioactivity. Herein, we used citric acid to synthesize carbon dots (CDs) and modified their surface properties by a variety of chemical conjugations to provide different functionalized CDs. It was found that dopamine-conjugated CDs can effectively inhibit hCT aggregation especially in the fibril growth phase and dissociate preformed hCT amyloids. Although the decomposition mechanism of dopamine-conjugated CDs is not clear, it seems to be specific to hCT amyloids. In addition, we also tested dopamine-conjugated mesoporous silica nanoparticles in preventing hCT fibrillization. They also can work as inhibitors but are much less effective than CDs. Our studies emphasized the importance of the size and surface functionalization of core materials in the development of nanomaterials as emerging treatments for amyloidosis. On the other hand, proper functionalized CDs would be useful in hCT formulation.

Dihydrocaffeic Acid-Decorated Iron Oxide Nanomaterials Effectively Inhibit Human Calcitonin Aggregation

“…The exposure of multiple catechol groups on carbon dots allows this water-soluble nanomaterial to effectively inhibit hCT fibrillization and disassemble preformed amyloid fibrils. 18 Similar approaches were used in this study to synthesize DO–Fe 3 O 4 . Irrespective of the dopamine-conjugated carbon dots or DO–Fe 3 O 4 , the stability of NPs is an important issue that needs to be addressed to achieve better efficacy.…”

“…The exposure of multiple catechol groups on carbon dots allows this water-soluble nanomaterial to effectively inhibit hCT fibrillization and disassemble preformed amyloid fibrils. 18 of NPs is an important issue that needs to be addressed to achieve better efficacy. With recent advances in surface chemistry for the fabrication of functional groups on iron oxide NPs, 27 it is possible to form extremely stable complexes of catechol ligands and carboxylic acid-based molecules with iron oxide NPs via an adsorption mechanism.…”

“…Compared to bare Fe 3 O 4 , DO−Fe 3 O 4 and DCA@ Fe 3 O 4 were more effective in dissociating mature fibrils. Although similar tests were performed in a previous study, 18 and the effectiveness of dopamine-conjugated carbon dots and Fe 3 O 4 were not directly compared; here, DO−Fe 3 O 4 appeared to perform better. Several minute fragments were only found in the hCT fibril samples upon the addition of DO−Fe 3 O 4 (Figure 5d).…”

“…hCT and IAPP in this study were both synthesized through a Liberty Lite microwave-assisted solid-phase peptide synthesizer with fluorenylmethyloxycarbonyl chemistry. A detailed description of peptide synthesis and purification has been described elsewhere. , Briefly, a low-loading Rink Amide ProTide Resin (CEM Corporation, 0.16 mmol/g) was used to work as solid-phase support and provided amidated C-terminus. 10% piperazine (w/v) in a solution of ethanol and N -methylpyrrolidone (10:90) was prepared as deprotection reagents and diisopropylcarbodiimide prepared in dimethylformamide worked as activation reagents in each cycle.…”

“…We have previously demonstrated that dopamine-conjugated carbon dots effectively inhibit hCT fibrillization. 18 Moreover, this nanomaterial with a size of less than 10 nm can also dissociate preformed hCT amyloids. The synthetic approach to creating carbon dots is simple and eco-friendly.…”