Targeted liposomes for cytosolic drug delivery to tumor cells

Abstract

In this thesis, a Trojan horse strategy with antibody-targeted liposomes has been followed to obtain cytosolic delivery of biotherapeutics to tumor cells in vitro. This strategy involves targeting of immunoliposomes to specific receptors on tumor cells that result in receptor-mediated uptake of the immunoliposomes. Escape of immunoliposome-entrapped biotherapeutics from within the endocytic compartment was realized by incorporating either influenza virus hemagglutinin proteins or synthetic dimeric fusion peptides resembling the fusion peptide domain of influenza virus HA into the immunoliposomes/virosomes. These molecules have membrane destabilizing and fusion activity at low pH allowing passage of liposome-entrapped drug over the endosomal membrane into the cytosol.Via the same cellular uptake route cationic polymer-condensed DNA could be specifically delivered into ovarian carcinoma cells by encapsulating polyplexes into antibody-targeted liposomes. The results demonstrate in vitro that liposomal delivery of biotherapeutics into the cytosol of target cells via the route of receptor-mediated endocytosis and subsequent endosomal escape is feasible and provide exciting new avenues to be explored in the future.