부산대학교 도서관

Antibiotic resistance (ABR) is a serious global health problem necessitating new bactericidal approaches as well as biosensors which can detect bacterial infection. Vesicular nanostructures have shown widespread promise for numerous biomedical applications in drug delivery and biosensing. A recently reported vesicle class composed of amphiphilic Janus dendrimers (AJDs), termed dendrimersomes (DSs), represent a promising system marrying the diverse chemistry of polymers and exact molecular definition of lipids. However, DSs have not yet been explored in depth for potential biomedical applications and, as yet, have not been used to construct nanoreactors - nanocompartments which encapsulate enzymes and permit reactions within a confined and localised space. Nanoreactors are of interest for myriad biomedical applications, some of which have been inspired by natural organelles. Herein, synthesis of a specific AJD was conducted and DS self-assembly investigated using various characterisation techniques revealing key properties of the DSs, particularly, their inherently semipermeable membranes, an essential property for use as a nanoreactor. Consequently, and inspired by the microbicidal function of the neutrophil phagosome, a DS-based nanoreactor was developed for an antibiotic-free bactericidal application. This was achieved by encapsulation of glucose oxidase and myeloperoxidase within DSs, enabling localised conversion of glucose to the highly potent microbicide, hypochlorite. This nanoreactor exerted a potent bactericidal effect against two bacterial pathogens on the WHO list for which new antibiotics are needed. Furthermore, a proof-of-concept is presented for harnessing the activity of membrane-lytic bacterial toxins to activate the nanoreactors through glucose release from separate lipid vesicles. Overall, the repertoire of potential DS biomedical applications has been expanded by this thesis and sets the basis for future nanoreactor applications. Lastly, again inspired by the activity of bacteria toxins, a liposome-based biosensor is presented towards the in vivo detection of Staphylococcus aureus lung infection using a colorimetric urinary readout. This system is composed of a liposome encapsulating renally clearable gold nanoclusters (AuNCs) with peroxidase-like activity. AuNC loading and in vitro release upon enzyme and toxin incubation was achieved and initial in vivo experiments performed to assess the utility of the system for detecting lung infection. Furthermore, initial work towards imparting an extra logic gate into the AuNC-liposome sensor for more specific disease detection is discussed. Overall, this thesis presents two vesicle-based systems towards treatment and detection of bacterial infection, which are in urgent need of alternative strategies due to the spread of ABR.