'Hide-and-Seek'- targeted drug delivery to intracellular pathogens

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Infectious diseases caused by pathogens such as bacteria, viruses and fungi are the second leading cause of death worldwide. Many pathogenic bacteria are capable of evading host defence mechanisms by hiding and replicating host immune cells, such as macrophages. From a therapeutic viewpoint, treatment of such infections can be very challenging, as many of current antimicrobial drug molecules do not efficiently cross plasma membrane of infected host cells, and thus cannot reach intracellular organelles where these pathogens are located. Thus, more effective strategies to address this clinical issue are urgently needed.This project will address this therapeutic problem by engineering drug delivery nanovectors able to target specific endocytic receptors in infected host cells and deliver antimicrobial agents to intracellular pathogens. One of the significant advantages of this approach is that it allows for the use of antimicrobial agents which would not normally cross the cell membrane of infected host cells, thus potentially expanding the range of available drugs to treat these infections, which can be key when therapeutic options are restricted due to antimicrobial resistance.Initially, this project will engineer targeted nanovectors by decorating liposomes with a range of ligands based on carbohydrates and/or short peptides - commercially available, and/or synthesised as part of this study. These nanovectors will incorporate fluorescent probes to facilitate their tracking in subsequent biomedical assays, and selected antimicrobial agents which will be tested on existing intracellular infection in vitro models.In this project the lipid composition of these nanovectors, the chemical nature, size and topology of ligands, and type of antimicrobial drug will be systematically varied to gain a first structure-activity relationship for these novel targeted nanomedicines.Project aligned to Advanced Product Design