Novel Cleavable PEGylated Liposomes for Enzyme Triggerable Release of Nucleic Acid in Tumours
P. Yingyuad, A. Miller, M. Thanou
Imperial College Genetic Therapies Centre, UK
Keywords: liposomes, triggerable release, nucleic acid delivery, tumours
Abstract:We have developed a dePEGylation approach based on the activity of the proteolytic enzymes that are associated with tumour cells. The elevated enzyme activity facilitates the extravasation of the cells by degrading the extracellular matrix barriers. We can take advantage of this enhanced enzymatic action to activate the dePEGylation and hence enhance liposomal fusion in order to improve the delivery of therapeutic agent directly to tumour cells. The aims of the project are to synthesize the PEGylated peptide-lipid by introducing a peptide linker, which is a specific enzyme substrate, between PEG polymer and a lipid and to develop enzyme-triggerable liposome containing the PEGylated peptide-lipid for nucleic acid delivery to tumour cells.