Endocytosis-mediated redistribution of antibiotics targets intracellular bacteria.

The increasing emergence and dissemination of antibiotic resistance pose a severe threat to overwhelming healthcare practices worldwide. The lack of new antibacterial drugs urgently calls for alternative therapeutic strategies to combat multidrug-resistant (MDR) bacterial pathogens, especially those that survive and replicate in host cells, causing relapse and recurrence of infections. Intracellular drug delivery is a direct efficient strategy to combat invasive pathogens by increasing the accumulation of antibiotics. However, the increased accumulation of antibiotics in the infected host cells does not mean high efficacy. The difficulty of treatment lies in the efficient intracellular delivery of antibiotics to the pathogen-containing compartments. Here, we first briefly review the survival mechanisms of intracellular bacteria to facilitate the exploration of potential antibacterial targets for precise delivery. Furthermore, we provide an overview of endocytosis-mediated drug delivery systems, including the biomedical and physicochemical properties modulating the endocytosis and intracellular redistribution of antibiotics. Lastly, we summarize the targets and payloads of recently described intracellular delivery systems and their modes of action against diverse pathogenic bacteria-associated infections. This overview of endocytosis-mediated redistribution of antibiotics sheds light on the development of novel delivery platforms and alternative strategies to combat intracellular bacterial pathogens.