PEGylation of dendronized silver nanoparticles increases the binding affinity of antimicrobial proteins

Abstract

Antibacterial resistance has become a global threat, and there is a pressing need for new antibacterial agents to treat bacterial infection. Silver nanoparticles (AgNPs) covered with cationic carbosilane (CBS) dendrons are promising nanomaterials thanks to their antibacterial activity and their ability to deliver antibacterial agents like antimicrobial proteins (AMP); lysozyme and bacteriophage endolysin. However, without an understanding and control of the nature of interactions between endolysin and dendronized AgNPs and affinity of serum proteins to NPs surface, the application of this multifunctional system in medicine and biology is limited. Herein, we investigate the interactions of PEGylated and non-PEGylated CBS dendronized AgNPs (PEG-Dend-AgNPs and Dend-AgNPs, respectively) with KP27 endolysin, lysozyme and human serum albumin (HSA) to check the binding mechanism and affinity between the NPs and proteins and the role of the PEG chain on the surface of dendritic silver nanoparticles. Analysis of binding mechanism with thermophoresis, fluorescence, thermodynamics, SPR and adsorption shows that endolysin and lysozyme have a higher affinity for PEG-Dend-AgNPs, whereas HSA has higher affinity to Dend-AgNPs. Lysozyme and endolysin create a monolayer “protein-PEG-Dend-AgNPs” corona and HSA creates a multilayer “protein-Dend-AgNPs”. These phenomena help to us to understand how surface modification is involved in the mechanisms of interaction of dendronized AgNPs with antimicrobial proteins (AMPs).This may help to develop new and better complexes of AMP-dendronized AgNPs acting against resistant bacteria with reduced affinity to serum proteins to improve their antimicrobial properties.