Nanoparticles Against Antimicrobial Resistance: Chemical Design, Assembly, and Emerging Applications

Abstract Antimicrobial resistance (AMR) is an escalating global health concern, with increasing rates of morbidity and mortality associated with multidrug-resistant infections worldwide. Despite intensive efforts to discover antimicrobial compounds, few candidates progress to clinical trials, and even fewer achieve market approval. A promising approach to address the current stagnation in antibiotic discovery is the development of advanced antimicrobial delivery platforms, which can enhance the efficacy, stability, and reusability of both existing and engineered antimicrobial agents. In this review, we provide an overview of the literature on the preclinical and clinical development of antimicrobial agents, as well as the integration of both existing and emerging agents into advanced delivery systems. These include inorganic nanoparticles (e.g., metal- and silicon-based) as well as (supramolecular) organic nanoparticles such as polymeric micelles, dendrimers, vesicles, polyelectrolyte complexes, hydrogels, lipid micelles, liposomes, lipid nanoparticles, emulsions, and hybrid formulations, among others. Using a soft matter science perspective, we discuss these nanoparticle scaffolds as platforms for incorporating antimicrobial compounds via encapsulation, conjugation, adsorption, entrapment, self-assembly, co-assembly, or driven-assembly strategies. While many of these delivery systems show substantial promise, key challenges, including technical limitations, toxicity, and immunogenicity, must be addressed before clinical translation. By reviewing recent advances and innovations, we highlight how nanotechnology-enabled delivery systems can overcome challenges posed by AMR and potentially shape the future of antimicrobial therapies.