Overview of nanotherapeutics for bacterial infections

The rapid emergence of antibiotic-resistant bacteria poses one of the greatest threats to public health as conventional therapies and commercial antibiotics are dropping their effectiveness. In the race for the discovery of new strategies to prevent a scenario in which commonplace infections prove fatal, nanomaterials stand in the limelight due to their unique physicochemical properties that can be seized to overcome common resistance mechanisms. Nanoparticle-driven drug delivery emerges as a beacon of hope, shielding antibiotics from enzymatic degradation, enhancing their targeted delivery to afflicted sites in therapeutically potent concentrations, and minimising undesired side effects. Drugs can either be entrapped or chemically conjugated to nanoparticles, with the latter offering a myriad of possibilities in orchestrating spatiotemporal controlled release of the therapeutic payload. Meanwhile, nanomaterials can also display intrinsic antimicrobial properties, either by direct disruption of bacterial cell membranes (e.g., nanoparticles functionalised with cationic groups) or by instigating the generation of ROS (e.g., metallic nanoparticles). The clinical implementation of nanotherapeutics still faces considerable challenges, mainly related with their complex chemistry and polydispersity, which poses difficulties related to cost-effectiveness, scale-up, and Chemistry, Manufacturing, and Controls (CMC) management. Still, the development of computational approaches allowing a better understanding of nano-bio interactions and predictive biodistribution, pharmacokinetics, and toxicology, along with a harmonised international regulatory framework, is expected to facilitate clinical translation in the near future.