4.6 Article

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

Journal

ACS OMEGA
Volume 7, Issue 35, Pages 31520-31528

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsomega.2c04206

Keywords

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Funding

  1. Ministry of Science and Technology, Taiwan [MOST MOST110-2113-M-003-021]

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More than 30 human peptides or proteins have been found to form amyloid fibrils, which are associated with various human diseases. However, there is currently no cure for amyloidosis. In this study, iron oxide nanoparticles were used to inhibit the aggregation of human calcitonin (hCT) and dissociate preformed amyloid fibrils, offering a potential therapeutic strategy for amyloidosis treatment.
To date, more than 30 human peptides or proteins have been found to form amyloid fibrils, most of which are associated with human diseases. However, currently, no cure for amyloidosis exists. Therefore, development of therapeutic strategies to inhibit amyloid formation is urgently required .Although the role of some amyloidogenic proteins has not been identified in certain diseases, their self-assembling behavior largely affects their bioactivity. Human calcitonin (hCT )is a hormone peptide containing 32 amino acids and is secreted by the parafollicular cells of the thyroid gland in the human body. It can regulate the concentration of calcium ions in the blood and block the activity of osteoclasts. Therefore, calcitonin has also been considered a therapeutic peptide. However, the aggregation of hCT hinders this process, and hCT has been replaced by salmon calcitonin in drug formulations. Recently, iron oxide nanomaterials have been developed as potential materials for various applications owing to their high biocompatibility, low toxicity, and ease of functionalization. In this study, nanoparticles (NPs) were prepared using a simple chemical coprecipitation method. We first demonstrated that dopamine-conjugated Fe3O4 inhibited hCTa ggregation, similar to what we found when carbon dots were used as core materials in the previous study. Later, we continued to simplify the preparation process, that is, the mixing of dihydrocaffeic acid (DCA) and iron oxide NPs, to maintain their stability and inhibitory effect against hCT aggregation. Furthermore, DCA-decorated Fe(3)O(4 )can dissociate preformed hCT amyloid fibrils. This appears to be one of the most promising ways to stabilize hCT in solution and ma ybe helpful for amyloidosis treatment.

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