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.
Highlights
Amyloid formation and accumulation have been shown to cause a wide range of diseases, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease [1]
Two Phe residues within this region have been suggested by solid-state nuclear magnetic resonance (NMR) study to stabilize β-sheets of Human calcitonin (hCT) amyloid fibrils via aromatic π-π interaction [25]
We found that the aggregation of hCT was accelerated in these two conditions including induction factors (Figure 4)
Summary
Amyloid formation and accumulation have been shown to cause a wide range of diseases, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease [1]. Human calcitonin (hCT), a 32-residue hormone peptide secreted from the parafollicular cells ( known as C-cells) of the thyroid gland, is one of the amyloidogenic proteins [3,4]. The main physiological function of calcitonin is the regulation of calcium and phosphate concentration in the blood. It has an opposite role to parathyroid hormone and reduces calcium levels in the blood through two main mechanisms: by inhibiting the activity of osteoclasts, which are the cells responsible for the bone breakdown, and by decreasing the resorption of calcium in the kidneys. Patients with medullary carcinoma of the thyroid may develop localized amyloid deposition in the tumors, but the cause is still unknown [6]. Due to the aggregation propensity of hCT, it is currently replaced by salmon calcitonin as an active pharmaceutical ingredient (API)
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