Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because
traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. To overcome this challenge,
we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded
with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm
poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid
supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag)
were taken up by macrophages, but not by non-phagocytic cells, such as fibroblasts, reducing non-specific
toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more
potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexigananloaded
NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse
whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver
and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising
strategy for the treatment of intracellular bacterial infection.