Bridging the translational divide: nanotechnological platforms for overcoming endolysin limitations against antibiotic-resistant infections

Abstract

Antibiotic resistance is a major global health threat, driving the need for alternative antimicrobial strategies. Bacteriophage-derived endolysins are promising agents due to their rapid and specific bactericidal activity, but their clinical application is limited by poor stability, short half-life, and inability to penetrate Gram-negative outer membranes. Nanotechnology-based delivery systems offer potential solutions to these limitations. This review summarizes recent advances in polymeric nanoparticles, liposomal systems, metal-based nanoparticles, and self-assembling peptides for enhancing endolysin efficacy. These platforms improve stability, bioavailability, and membrane penetration while enabling controlled and targeted delivery. Despite promising preclinical outcomes, clinical translation remains limited due to regulatory, manufacturing, and immunological challenges. Addressing these barriers is essential for advancing nanotechnology-enhanced endolysins toward clinical application.