Design of nanocarriers for hexadentate 3,4-hydroxypyridinone chelators: A macrophage-targeted strategy to address intracellular infections

Iron deprivation is a promising and alternative approach to fight mycobacterial infection, exploiting bacteria's dependence on iron for survival and proliferation. In our previous studies, the use of rhodamine labelled 3,4-hydroxypyridinone Fe chelators was effective to control the intramacrophagic growth of Mycobacterium avium . However, it is expected that the cytocompatibility and the targeting of macrophages can be improved. To reach this aim, the next studies considered the encapsulation and targeted delivery of non-labelled hexadentate iron chelators (CP256 and MRHT) using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The present study demonstrates that the compounds were efficiently loaded into PLGA nanoparticles, without losing the iron chelating properties of the chelators, and that the NPs were internalised by macrophages. These findings highlight the potential of drug delivery systems in the development of new strategies to address bacterial infections, particularly those involving intracellular pathogens resistant to conventional therapies. • Iron deprivation is taken as promising alternative to fight bacterial infections. • Two iron chelators were successfully loaded into polymeric nanoparticles. • Mannose-functionalized polymeric nanoparticles (NPs) were obtained. • Functionalized NPs improved the delivery of iron chelators to macrophages. • Newly obtained NPs may enhance efficacy against intracellular bacterial growth.