Wearing bacteriophages individually with an adhesive drug-loadable nanohelmet for treating ocular infections

Ocular infections pose notable blindness risks. Despite its advantages in inhibiting multidrug-resistant bacteria and eliminating biofilms, phage therapy suffers low phage vitality, limited ocular retention, and lack of anti-inflammatory abilities toward ocular infections. Here, wearing phages individually with an adhesive drug-loadable nanohelmet is reported to advance phage therapy. The nanohelmet is formed by depositing arginine-glycine-aspartic acid-modified chitosan on negatively charged phage head through electrostatic interactions, followed by codepositing anti-inflammatory agents via physical adsorption. Nanohelmet formation shows a negligible influence on phage vitality and is applicable to helmet diverse phages. Because of the cationic nature and the presence of arginine-glycine-aspartic acid sequence, such nanohelmet exhibits a double-lock adhesion fashion to ocular surface, prolonging phage retention after instillation. Together with sustained drug release, helmeted phages potently inhibit bacteria, eliminate biofilms, and effectively suppress localized inflammation. In mice with multidrug-resistant pathogen-induced keratitis, helmeted phages achieve superior therapeutic efficacies, even compared to clinical therapeutics.