Advances in the production, purification, and concentration of bacteriophage bionanoparticles for biomedical applications

Bacteriophage (phage) colloidal bionanoparticles garnered significant interest in colloid and interface science for their unique structural, interfacial, and self-assembly properties, as well as their potential for biomedical applications. The global rise of drug-resistant bacteria presented an urgent global health challenge, contributing to millions of deaths annually. Phages offered a promising alternative to antibiotics due to their high specificity and minimal side effects, and they also found diverse applications in environmental disinfection, food safety, and biomaterial engineering. However, large-scale phage manufacture remained a considerable challenge due to the complexity of production pipelines and the need to control contaminants that could compromise both safety and efficacy. In this review, we provided a comprehensive overview of phage acquisition, identification, and propagation methods, followed by an in-depth examination of advanced approaches for phage concentration and purification. We particularly emphasized how colloidal and interfacial phenomena could be leveraged to optimize the stability and functionality of phage colloidal bionanoparticles. We further presented an integrated framework for enhancing phage purification processes to ensure high bioactivity and broad applicability in clinical and industrial contexts. Lastly, we highlighted the need for tailoring propagation and purification protocols to specific phages to meet increasing demands for tissue regeneration, disease therapy, and beyond. By addressing these interdisciplinary challenges, this review underscored the substantial promise of phage colloidal bionanoparticles in generating significant economic and societal benefits.