Enhancing the therapeutical potential of metalloantibiotics using nano-based delivery systems

The rapid spread of antibiotic resistance has intensified the need for novel therapeutic strategies against multidrug-resistant bacterial infections. Metalloantibiotics present a promising alternative in combating resistant pathogens. However, the clinical application of metalloantibiotics is limited by their potential toxicity, instability, and lack of target specificity. Encapsulating metalloantibiotics in drug delivery systems, such as liposomes, nanoparticles, and polymeric carriers, could mitigate these challenges, enhancing their therapeutic index and enabling their precise, localized release. Recent reviews have outlined the key design parameters and clinical translation challenges associated with nanocarrier-based antimicrobial therapies, underscoring their relevance in overcoming bacterial resistance mechanisms [Xie, Y.; Liu, H.; Teng, Z.; Ma, J.; Liu, G. Nanoscale 2025, 17, 5605-5628. https://doi.org/10.1039%2FD4NR04774E ]. This review explores the potential of encapsulated metalloantibiotics as a new frontier in antimicrobial therapy. We address the mechanisms by which drug delivery systems can stabilize and direct metalloantibiotics to their biological targets, discuss current advancements in encapsulation methods, and examine the efficacy of encapsulated metalloantibiotics. Finally, we consider the challenges and future directions for the integration of metalloantibiotic-loaded carriers in the fight against antibiotic-resistant infections.