Toxin-responsive metal-organic framework nanocarriers for precision delivery of antimicrobial peptides against drug-resistant infections

Antimicrobial resistance has emerged as a major global healthcare challenge owing to the rapid rise in multidrug-resistant bacterial infections and the declining effectiveness of conventional antibiotics. Antimicrobial peptides have gained considerable attention as alternative therapeutic agents because of their broad-spectrum antimicrobial activity, membrane-targeting mechanisms, immunomodulatory functions, and reduced susceptibility to resistance development. The clinical translation of antimicrobial peptides is limited by enzymatic degradation, poor stability, rapid clearance, systemic toxicity, and inefficient infection site targeting. In this context, metal-organic frameworks have emerged as effective nanocarriers for precision antimicrobial peptide delivery owing to their tunable porosity, high loading capacity, surface functionalization, and stimuli-responsive behavior. This review comprehensively discusses the molecular mechanisms of antimicrobial peptides, engineering strategies for metal-organic framework-based delivery systems, and toxin-responsive nanocarrier designs for selective antimicrobial therapy. Different toxin-responsive approaches, including lipid bilayer-disruptable systems, membrane-coated toxin-decoy metal-organic frameworks, phospholipase-triggered platforms, virulence-factor-amplified systems, and dual-responsive nanocarriers, are highlighted for their ability to achieve site-specific antimicrobial peptide release in pathogen-rich microenvironments. Furthermore, recent in vitro , in vivo , and preclinical studies demonstrating therapeutic efficacy against multidrug-resistant and biofilm-associated infections are reviewed. Toxin-responsive metal-organic framework nanocarriers represent an advanced precision nanomedicine strategy with considerable potential for combating drug-resistant bacterial infections.