Abstract
The increasing prevalence of bacterial resistance to conventional antimicrobial agents and nanoparticles (NPs) has become a critical global health challenge. This systematic review aimed to evaluate strategies for overcoming bacterial resistance to nanoparticles by synthesizing evidence on nanoparticle composition, functionalization, and targeted resistance mechanisms. A comprehensive literature search of studies published between 2000 and 2025 was conducted, focusing on experimental designs assessing antimicrobial efficacy, biofilm disruption, and efflux pump inhibition. The reviewed studies highlighted advanced nanoparticle formulations, including silver-cyanographene conjugates, lanthanum-functionalized graphene oxide, and carbon nanogels, which demonstrated enhanced efficacy against resistant bacterial strains. Key findings emphasized the role of surface functionalization, nanoparticle size modulation, and combination therapies in mitigating resistance. Functionalized nanoparticles effectively disrupted biofilm matrices, inhibited efflux pumps, and enhanced intracellular penetration, reducing bacterial survival rates. Despite promising results, challenges remain, including variability in nanoparticle formulations, limited scalability, and long-term ecological impacts. This review underscores the potential of innovative nanoparticle designs and combination therapies to combat bacterial resistance and emphasizes the need for standardized protocols and clinical translation.