Student award winner in the Ph.D. category for the 2013 society for biomaterials annual meeting and exposition, april 10–13, 2013, Boston, Massachusetts 1: Biomaterial‐mediated cancer‐specific DNA delivery to liver cell cultures using synthetic poly(beta‐amino ester)s. Issue 7 (5th April 2013)

• Record Type: Journal Article
• Authors: Tzeng, Stephany Y.; Higgins, Luke J.; Pomper, Martin G.; Green, Jordan J.
• Is Part Of: Journal of biomedical materials research. Volume 101A:Issue 7(2013:Oct.)
• Page Start: 1837
• Page End: 1845
• Publication Date: 2013-04-05
• Subjects: non‐viral gene therapy -- nanoparticles -- drug delivery -- liver cancer -- DNA; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/jbm.a.34616
• Languages: English
• ISSNs: 1549-3296

Abstract

Abstract: 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 ester)s (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 < 0.05 for both percentage transfected and eGFP expression intensity). Top polymers from eGFP studies also delivered luciferase DNA with 220 ± 30‐fold and 470 ± 30‐fold greater specificity for hepatoma cells than hepatocytes. Transfections of co‐cultures of hepatoma and hepatocytes with eGFP DNA also showed high specificity (1.9 ± 0.1‐ to 5.8± 1.4‐fold more transfected hepatoma cells than hepatocytes, measured by percentage transfected and flow cytometry). By eGFP intensity, up to 530 ±60‐fold higher average expression per cell was measured in hepatoma cells. One top formulation caused (95 ± 0.2)% transfection in hepatoma cells and (27 ± 0.2)% in hepatocytes [(96 ± 9)% relative hepatocyte viability]. PBAE‐based nanoparticles are a viable strategy for liver cancer treatment, delivering genes to nearly 100% of cancer cells while maintaining high biomaterial‐mediated specificity to prevent toxic side‐effects on healthy hepatocytes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.