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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43934127" target="_blank" >RIV/60461373:22340/20:43934127 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.colsurfa.2019.124279" target="_blank" >https://doi.org/10.1016/j.colsurfa.2019.124279</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.colsurfa.2019.124279" target="_blank" >10.1016/j.colsurfa.2019.124279</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS

ISSN

0927-7757

e-ISSN

1873-4359

Svazek periodika

586

Číslo periodika v rámci svazku

5 February 2020

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

nestránkováno

Kód UT WoS článku

000504350600010

EID výsledku v databázi Scopus

2-s2.0-85076220295