Functionalized nanoparticles for the precise treatment and prevention of bacterial infections

Multidrug-resistant (MDR) bacterial infections are an escalating health issue, and their rise poses a major threat worldwide. Inappropriate antibiotic use, including unnecessary prophylaxis, and nonpathogen-directed therapy, accelerates resistance, diminishing the effectiveness of conventional antibiotics. Consequently, novel antimicrobial strategies are urgently required to achieve precise prevention and treatment of bacterial infections while minimizing selective pressure for resistance. Nanotechnology-based antimicrobials are promising candidates because of their unique advantages: payload concentration at infection sites, biofilm penetration and disruption, synergism with conventional antibiotics, and modulation of host immunity via innate/adaptive immune activation (e.g., macrophage polarization, dendritic cell maturation, and immunogenic cell death induction). This review describes the current classifications and antibacterial mechanisms of nanoantibacterial agents and summarizes strategies for targeted antibacterial and immunoregulatory nanoparticle therapies. We also identify key translational challenges, including safety and immunotoxicity, biodistribution and clearance, microbiome and environmental impacts, scalable manufacturing, assay standardization, regulatory issues, and clinical validation. Finally, we outline future directions, such as rational design of stimulus-responsive nanocarriers, data-driven optimization, theranostics, and clinically aligned evaluation. These efforts aim to advance nanoantibacterials that complement antibiotics, enabling precise MDR infection management, thereby bridging the gap between prevention and treatment to address the global antimicrobial resistance crisis.