The emergence of
drug-resistant pathogens causes the greatest challenge for
drug development research. Recently,
gallium(III)-based compounds have received great attention as novel
antimicrobial agents against
drug-resistant pathogens. Here, we synthesized a new β-
cyclodextrin Ga nanoparticle (CDGaTP) using Ga
tetraphenylporphyrin (GaTP, a
hemin analogue) and β-
cyclodextrin. The newly synthesized nanoparticle was nontoxic and efficient at a single dose, showing sustained drug release for 15 days in vitro. CDGaTP's activity with
transferrin or
lactoferrin was tested, and synergism in activity was observed against nontuberculosis mycobacteria (NTM), Mycobacterium avium (M. avium), and Mycobacteroides abscessus.
Human serum albumin (HSA) decreased the efficacy of both GaTP and CDGaTP in a concentration-dependent manner. The NTMs incubated with GaTP or CDGaTP significantly produced
reactive oxygen species (ROS), indicating potential inhibition of
antioxidant enzymes, such as
catalase. The single-dose CDGaTP displayed a prolonged intracellular inhibitory activity in an in vitro macrophage
infection model against both NTMs. In addition, CDGaTP, not GaTP, was effective in a murine lung M. avium
infection model when delivered via
intranasal administration. These results suggest that CDGaTP provides new opportunities for the development of
gallium-
porphyrin based
antibiotics.