Nanoparticle carriers in the treatment of intracellular bacterial infections: Current approaches and challenges

Pathogenic bacterial intracellular infection by Mycobacterium tuberculosis and Staphylococcus aureus is a major complication to treatment because of resistance to immune actions and the ability to withstand traditional antibiotics. Failure of existing therapies is usually due to inefficient intracellular penetration of drugs and inappropriate targeting of subcellular sites. We discuss the nanoparticle drug delivery systems (NDDSs) here that enhance intracellular delivery of antibiotics using customized carrier materials, targeted internalization processes and stimuli-responsive release of antibiotics. These systems enhance specificity of pathogen targeting and efficacy of drugs and overcome barriers of microenvironment. We also address translational challenges such as toxicity, heterogeneity of infection, scalability of manufacturing, and scanty clinical data. Future trends include versatile hybrid vehicles, combination with immunomodulators or gene-editing applications and AI-enhanced personalized nanomedicine. The potential to tackle pathogen-specific issues with nanotechnology advances can provide possible solutions to the treatment of persistent intracellular infections and antibiotic resistance, which are the prospects with NDDSs.