Inhibition of amyloid fibrillation, enzymatic degradation and cytotoxicity of insulin at carboxyl tailored gold-aryl nanoparticles surface

Autor: Mohamed M. Chehimi, Mehavesh K Hameed, Nemat D. AlBab, Aneta Maresova, Ahmed A. Mohamed, Bizuneh Workie, Mahreen Arooj, Islam M. Ahmady, Changseok Han
Rok vydání: 2020
Předmět:
Zdroj: Colloids and Surfaces A: Physicochemical and Engineering Aspects. 586:124279
ISSN: 0927-7757
DOI: 10.1016/j.colsurfa.2019.124279
Popis: Insulin fibrillation complicated its oral delivery in diabetes therapy. pH sensitive carboxylate-terminated gold-carbon nanoparticles, AuNPs-C6H4-4-COOH, inhibited amyloid fibrillation and disintegrated the preformed insulin fibrils under amyloidogenic conditions. Transmission electron microscopy and X-ray photoelectron spectroscopy results support the immobilization of insulin on the nanoparticles surface. In contrast to native insulin, gold insulin bioconjugate exhibited a significant inhibitory effect against the proteolytic enzymatic activity of pepsin and trypsin while passaging through the stomach and gastrointestinal tract. Fluorescence solution studies supported the insulin fibrils dissociation over the gold nanoparticles surface in the presence of thioflavin T dye. In addition, fluorescence quenching studies were carried out to estimate the binding constant and the number of binding sites in insulin available for the gold nanoparticles. The outstanding hemocompatibility of the insulin bioconjugate in the presence of diabetic and non-diabetic red blood cells supports its significance in insulin drug delivery. With the aid of molecular docking calculations, we were able to verify the mediation of hydrophobic and hydrogen bonding interactions of benzoic acid with the fibril-forming region of insulin, which prevents these residues from the unfolding necessary for fibrillation. The robust gold-carbon nanoparticles mediation can be extended to defibrillate other proteins with nanomedicine therapies in Alzheimer’s, Parkinson’s, Huntington’s and infectious prion diseases.
Databáze: OpenAIRE