New trends in antimicrobial therapy: from chemical innovation to physical synergistic enhancement

The escalating crisis of antimicrobial resistance calls for a paradigm shift that moves beyond conventional chemical agents. In response, the field of antimicrobial nanomaterials has advanced significantly. It has diversified into various forms, including intelligent nanocarriers for antibiotic delivery, as well as metal-based, organic, and hybrid nanoparticles with intrinsic antimicrobial activity. Furthermore, the field now also covers active agents that can be triggered by external physical stimuli, such as photothermal or ultrasonic fields, and those with distinctive morphological characteristics. In this review, we move beyond simple material cataloging by proposing a " Synergy Framework" that systematically reclassifies emerging strategies according to their dominant functional modality: (i) physical-disruption modalities (e.g., nano-topography and exogenous energy triggers), (ii) chemical-intelligent modalities (e.g., stimuli-responsive drug release and ROS). Special attention is given to how the combination of physical stimuli with advanced functional materials can work in synergy to enhance host immune responses and achieve precise disruption of drug-resistant biofilms, thereby facilitating efficient clearance of infection sites.