Selective accumulation of nanoparticles in infected cells for targeted drug delivery

In response to the escalating threat of infectious diseases and antimicrobial resistance, novel therapeutic strategies are under active development. Among them, nanoparticle-based systems offer promising avenues for targeted antimicrobial delivery. In pulmonary infections, aerosolized nanocarriers can improve local biodistribution while limiting systemic exposure and side effects. Here, we show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles, administered intranasally to Mycobacterium tuberculosis-infected mice, distribute broadly throughout the lungs and preferentially accumulate in alveolar macrophages, the primary host cells of the pathogen. Remarkably, infected macrophages internalize significantly more nanoparticles than uninfected cells, resulting in higher intracellular drug levels and improved targeting of the infectious agent. This preferential uptake is consistent across models of bacterial, viral, and parasitic infections, and with various nanomaterials. Collectively, these findings reveal a striking feature of drug delivery systems: their capacity to selectively accumulate in infected cells, offering a powerful strategy to enhance antimicrobial delivery precisely where it is most needed.