Phage Receptor-Binding Proteins for Targeted Silver Nanoparticle Delivery: Design and Evaluation

Antimicrobial resistance has renewed interest in silver nanoparticles (AgNPs), but limited pathogen selectivity complicates their therapeutic use. Bacteriophage receptor-binding proteins (RBPs) recognize bacterial surface receptors and offer candidate targeting modules for AgNP delivery. However, evidence from intact-phage composites and non-silver carriers cannot establish the performance of isolated RBP-AgNP systems. In this review, we link RBP architecture and receptor recognition to ligand selection, orientation and multivalent display on AgNPs. We outline workflows for RBP discovery and receptor assignment, review conjugation strategies, and examine how Ag⁺ release and oxidative stress contribute to antibacterial activity. We propose a dual-endpoint framework to quantify nanoparticle enrichment near target bacteria and test for bactericidal gain using receptor-level controls, matched total silver doses and measurements of silver release. We discuss protein-corona masking, receptor variation and activity retention in complex infection settings, including biofilms, alongside manufacturing reproducibility. Translation further requires formulation-specific assessment of in vivo exposure, host tolerance, environmental fate and ecological risk. This framework defines the evidence needed to determine whether RBP-guided delivery improves antibacterial efficacy and safety.