Reversible and biocompatible AuNP-decorated [Zn2+]:[Insulin] condensed assembly for potential therapeutic applications

Eur J Pharm Sci. 2022 Jun 1:173:106168. doi: 10.1016/j.ejps.2022.106168. Epub 2022 Mar 19.

Abstract

The present study reports the construction of Gold Nanoparticle (AuNP)-decorated [Zn2+]:[Insulin] condensed assembly which was found to be reversible and biocompatible. At first, Citrate-Capped AuNPs were synthesized using the Turkevich method, and the colloidal solution was co-incubated with [Zn2+]:[Insulin] maintaining an equimolar stoichiometry, at physiological pH, 60 °C and 6 h. Accordingly, the effect of excess Zn2+ and surface sorption events were investigated. The surface chemistry of protein sorption on AuNPs involved interaction of surface citrate with the amyloidogenic residues of insulin Chain A (L13, E17, N18) and Chain B (V12, Y16, L17), and also C7:A, C7:B, C20:A. The surface sorption involved a number of driving forces which were predicted to be covalent, H-bonding and hydrophobic interactions. Upon the capture of a fraction of insulin molecules, the Zn2+ was found to form cross-links between the unbound monomers and insulin bound on AuNP, thus forming nucleating species with dendritic morphology. The dendritic species self-assembled into linear and branched organization, followed by the formation of densely packed AuNP-decorated [Zn2+]:[Insulin] condensed assembly. Subsequently, alteration of pH resulted in changes of local charges, thus destabilizing the intermolecular ionic interactions, and subsequently caused the reversal of the condensed assembly back to monomeric forms. Furthermore, the reversible AuNP-decorated [Zn2+]:[Insulin] condensate was found to be biocompatible, and promoted the growth of the adherent cell line, BHK-21 fibroblasts. The non-cytotoxic and reversible material thus formed might have enormous applications in bioelectronics, cell culture matrices, and drug-delivery systems.

Keywords: Citrate-Capped AuNP; Reversible assembly; Self-assembly; Surface sorption; [Zn(2+)]:[Insulin].

MeSH terms

  • Citric Acid
  • Gold* / chemistry
  • Insulin
  • Metal Nanoparticles* / chemistry
  • Zinc

Substances

  • Insulin
  • Citric Acid
  • Gold
  • Zinc