Targeted delivery of macromolecules using a novel virus-mimicking liposomal system

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The efficient intracellular delivery of therapeutic molecules using liposomal systems has been of interest for many years. However, issues remain with regards to the successful delivery of macromolecules using liposomes, which cause quick elimination of the delivery system from the bloodstream or induction of an immune response, affecting the efficacy of the payload. The use of non-viral vectors can address this issue as they have the ability to mimic viruses, hence allowing evasion of the mononuclear phagocyte system (MPS), which in turn allows circulation times of up to one week as well as enhanced treatment of the targeted tumour (Geng et al., 2007; Niu et al., 2013). Chen et al. have developed polymers that mimic the activity of viral fusogenic peptides with the novelty of being pH-responsive (Chen et al., 2017). Preliminary work carried out by the group shows promising results with regards to the successful intracellular delivery of macromolecules such as nucleic acids and proteins. This could be beneficial for more targeted delivery of drugs and therapeutic molecules to treat diseases such as cancer. Another area of interest is to prolong the shelf life, enhance targeting capacity and improve controlled release of such liposomal drug delivery systems (Payton et al., 2014). The ability to store these delivery systems for a longer amount of time, without the loss of stability and functionality, would be very beneficial not only to protect the payload, but also economically, to commercialize these systems within industry.The aim of this project is to synthesise a novel virus-mimicking liposomal delivery system using pH-responsive polymers developed by Chen et al. as the surface coating (Chen et al., 2017). The system will be optimised for more controllable and targeted intracellular delivery of macromolecules such as proteins and nucleic acids into a range of different cell types, including cancer cell lines. The ability for the system to cross the cell membrane, successfully release the payload, and ultimately trigger apoptosis will be assessed. Moreover, the storage method of these delivery systems will be optimised to allow for longer storage at room temperature without compromising the integrity of the system.