Biomaterial-mediated cancer-specific DNA delivery to liver cell cultures using synthetic poly(beta-amino esters)

• Published in: Journal of biomedical materials research. Part A 2013-04, Vol.101 (7), p.1837-1845
• Main Authors: Tzeng, Stephany Y., Higgins, Luke J., Pomper, Martin G., Green, Jordan J.
• Format: Article
• Language: English
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.34616

Liver cancer is a leading cause of cancer death. Most patients are treated by arterial injection of chemoembolizing agents, providing a convenient avenue for local treatment by novel therapies, including gene therapy. Poly(beta-amino esters) (PBAEs) were synthesized and used to form nanoparticles for non-viral transfection of buffalo rat hepatoma (MCA-RH7777) and hepatocyte (BRL-3A) lines with eGFP and luciferase DNA. Hepatoma cells were transfected with up to 98±0.4% efficacy with no measurable cytotoxicity. Hepatocytes were transfected with as high as 73±0.4% efficacy with 10±4% non-specific cytotoxicity. In contrast, positive controls (branched polyethylenimine, Lipofectamine ™ 2000, and X-tremeGENE® DNA HP) caused 30–90% toxicity in BRL-3A cells at doses required for >50% transfection. Of the 21 optimized PBAE-DNA formulations tested, 12 showed significant specificity for hepatoma cells over hepatocytes in monoculture ( P