M-PEIs nanogels: potential nonviral vector for systemic plasmid delivery to tumor cells.
Successfully systemic gene therapy has been hindered by vector-related limitations, including toxicity and inefficient gene delivery to tumor cells after intravenous administration. In this study, we evaluated the potential of spherical polyethylenimine nanogels (M-PEIs) as a novel vector for intravenous delivery of plasmids to tumor cells. M-PEIs provided a sustained release of plasmids up to 14 days and were also effective in protecting plasmids from enzymatic degradation in serum-conditioned media. M-PEIs showed no obvious cytotoxicity to mammalian cells in vitro as well as to liver, heart and kidney in mice after intravenous injection. Importantly, following intravenous administration of M-PEIs/plasmid complexes into human hepatocellular carcinoma xenograft-bearing mice, green fluorescence protein reporter gene expression was predominantly found in the tumor. This study indicates that M-PEIs may be a candidate for systemic delivery of plasmids into tumors.