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

Stephany Y. Tzeng, Luke J. Higgins, Martin G. Pomper, Jordan J. Green

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1837-1845
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume101 A
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • DNA
  • drug delivery
  • liver cancer
  • nanoparticles
  • non-viral gene therapy

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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