Antimicrobial Nanoparticles Against Resistant Bacteria and Biofilms: From Material Design to Clinical Translation

Antimicrobial resistance (AMR) and biofilm-associated infections continue to compromise the effectiveness of conventional antibiotics, highlighting the need for complementary therapeutic approaches. Nanoparticle-based systems offer two distinct but potentially convergent strategies: direct antibacterial activity and improved delivery of antimicrobial agents. This narrative review critically examines inorganic, organic, and hybrid nanoplatforms, including metal and metal-oxide nanoparticles, carbon-derived materials, mesoporous silica, polymeric carriers, lipid-based systems, and stimuli-responsive formulations. Their mechanisms of action, physicochemical determinants of efficacy, and potential applications against multidrug-resistant bacteria and biofilm-associated infections are discussed. Particular attention is given to the distinction between bacterial resistance, tolerance, and persistence, as well as the challenges associated with nanoparticle penetration, antimicrobial synergy, and reproducible antibacterial activity. Although preclinical findings demonstrate considerable therapeutic potential, translation into clinical practice remains limited. Inhaled liposomal amikacin illustrates the clinical relevance of indication-specific nanodelivery, while emphasizing that therapeutic benefits cannot be generalized across nanoparticle formulations. Major challenges include cytotoxicity, bacterial adaptation, biodistribution, stability in biological environments, manufacturing scalability, regulatory requirements, and environmental safety. Future research should prioritize standardized characterization, clinically relevant infection models, robust comparisons with conventional treatments, and integrated assessments of safety and resistance evolution. Within a One Health framework, nanoparticle-based technologies may contribute to more effective antimicrobial therapies, provided that their development is guided by demonstrable clinical benefits, responsible antimicrobial use, and consideration of their broader environmental impact.