Nanomaterial strategies for antibiotic-resistant infections: Mechanistic frameworks, rational design, and clinical translation.

Antimicrobial resistance drives substantial global morbidity and mortality, yet conventional antibiotics often fail in rapidly disseminating planktonic bloodstream infections or sepsis, intracellular reservoirs with limited drug exposure, and biofilm- or device-associated infections that are prone to relapse. Nanomaterials provide an interface-focused, multitarget approach that combines direct antibacterial activity, controlled delivery, and host modulation. Here, we evaluate antibacterial nanomaterials according to the major biological barriers encountered during the infection cascade, including surface precolonization, adhesion and invasion, biofilm maturation, intracellular persistence, and tissue spread or relapse. These barriers correspond to material functions such as membrane permeabilization, proton-motive-force and efflux modulation, matrix penetration and remodeling, intracellular release, and host-directed immunomodulation. Current strategies broadly include intrinsically antibacterial materials and nanocarriers that enhance the activity of existing antibiotics through controlled release or externally triggered activation. Evidence is evaluated through quantitative readouts linking mechanisms to outcomes, including bacterial burden reduction, biofilm remodeling, intracellular clearance, and relapse-related endpoints. We also discuss diagnostic and image-guided systems, together with translational requirements such as reproducible manufacturing, controlled ion or reactive oxygen species release, predictable protein-corona behavior, infection-site pharmacokinetics, and regulatory alignment beyond the