Abstract
Gene and nucleic acid therapy are expected to play a major role in the next generation of medicine. We recently developed a multifunctional envelope-type nano device (MEND) for use as a novel non-viral gene delivery system. PEGylation is a useful method for achieving a longer circulation time for delivery of the MEND to a tumor via the EPR effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results significant loss of activity for the delivery system. For successful gene delivery for cancer treatment, the crucial issue associated with the use of PEG, the "PEG dilemma" must be solved. Here, we describe the development and applications of MEND, and discuss strategies for overcoming the PEG dilemma, based on the manipulation of intracellular trafficking using functional devices such as cleavable PEG systems, endosomal fusogenic peptides, and pH-sensitive lipids.
