Treatment of individuals coinfected with human immunodeficiency virus (HIV) type 1 and Mycobacterium tuberculosis is challenging due to the prolonged treatment requirements,
drug toxicity, and emergence of drug resistance. Mononuclear phagocytes (MP; macrophages) are one of the natural reservoirs for both HIV and M.
tuberculosis Here, the treatment of HIV and M.
tuberculosis coinfection was studied by preloading human macrophages with MP-targeted
gallium (Ga) nanoparticles to limit subsequent simultaneous
infection with both HIV and M.
tuberculosis Ga nanoparticles provided sustained drug release for 15 days and significantly inhibited the replication of both HIV and M.
tuberculosis Addition of Ga nanoparticles to MP already infected with M.
tuberculosis or HIV resulted in a significant decrease in the magnitude of these
infections, but the magnitude was less than that achieved with nanoparticle preloading of the MP. In addition, macrophages that were coinfected with HIV and M.
tuberculosis and that were loaded with Ga nanoparticles reduced the levels of
interleukin-6 (IL-6) and
IL-8 secretion for up to 15 days after drug loading. Ga nanoparticles also reduced the levels of
IL-6 and
IL-8 secretion by
ionomycin- and
lipopolysaccharide-induced macrophages, likely by modulating the IκB
kinase-β/NF-κB pathway. Delivery of Ga nanoparticles to macrophages is a potent long-acting approach for suppressing HIV and M.
tuberculosis coinfection of macrophages in vitro and sets the stage for the development of new approaches to the treatment of these important
infections.