Nanomedicine against antimicrobial resistance: mechanistic insights and next-generation therapeutic potential

Abstract

Antimicrobial resistance (AMR) has emerged as one of the most critical global health threats, severely limiting the effectiveness of existing therapies against bacterial, fungal, and viral infections. The increasing prevalence of multidrug-resistant pathogens is largely driven by rapid genetic evolution, which promotes multiple resistance mechanisms such as drug degradation, target-site alteration, reduced intracellular drug accumulation, and biofilm formation, leading to persistent infections and rising mortality. These challenges highlight the urgent need for alternative therapeutic strategies beyond conventional antimicrobials. Nanomedicine has gained considerable attention due to its unique physicochemical properties, enabling improved drug stability, targeted delivery, controlled release, enhanced pathogen penetration, and multimodal antimicrobial action. This review comprehensively examines resistance mechanisms across major microbial pathogens and discusses the evolution of nanomedicine as an advanced platform for combating AMR. Particular emphasis is placed on green biogenic synthesis of nanoparticles using biological resources, offering environmentally sustainable and biocompatible antimicrobial nanomaterials. The synergistic interactions between nanomaterials and conventional antimicrobial agents that enhance therapeutic efficacy and restore susceptibility in resistant pathogens. Emerging next-generation antimicrobial nanomedicine platforms, including biomimetic nanoparticles, antimicrobial peptide delivery systems, CRISPR-enabled nanocarriers, and stimuli-responsive systems, are also highlighted for their potential in precision infection management. Finally, key challenges involving toxicity, biosafety, microbiome disruption, environmental impact, manufacturing scalability, regulatory and clinical translation. Addressing these barriers will be essential for advancing safe and effective nanomedicine-based solutions against AMR.