Reframing antibacterial strategies through physical targeting: Mechanisms and future directions

Development of novel antibacterial techniques and targeting is essential due to increased antibiotic resistance of bacteria. Nano- and microparticles (MPs) provided a viable platform that addresses the limitations of conventional antibacterial treatments. However, bacterial resistance has developed against these materials by preventing nanoparticle diffusion through biofilms, efflux and intracellular signalling alteration. Therefore, engineering the physical properties of nano/microparticles to address these limitations is essential. Namely, by benefiting from physical principles, pH-responsive zwitterionic nanoparticles that undergo charge reversal from negative to positive within biofilm's microenvironment have facilitated deeper penetration and enhanced interaction with bacteria. These observations indicate that resistance is not only a genetic or biochemical, but also a physical interaction phenomenon. Targeting is a critical factor in diverse applications, from environmental to biological, for increasing treatment efficiency. Among different targeting methods, physical methods are known as low-cost, reproducible and compatible with large-scale production. Accordingly, the current review focuses on the physical properties of nano/microparticles and how they modulate interaction with bacteria. We highlight how physical characteristics, such as size and shape, enhance particle penetration into biofilm and boost contact with bacterial membrane. Bioinspired approaches such as imprinting of pathogenic bacteria are discussed as physical targeting tools. These advancements position engineered nano/microparticles as the next-generation of antimicrobial agents, harnessing physical interactions to fulfill the urgent need for alternative treatments.