Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer

Soo Hyun Jang, Su Jin Choi, Ji Hyun Oh, Song Wha Chae, Kihoon Nam, Jong Sang Park, Hwa Jeong Lee

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: A specific and effective strategy is in demand to treat ovarian cancer successfully. Epidermal growth factor receptor (EGFR) is highly expressed in ovarian cancer, and thus EGFR antisense gene therapy can be a potential therapeutic strategy. Method: l-Arginine-grafted-polyamidoamine dendrimer (PAMAM-Arg) has been reported to be a novel nonviral gene delivery carrier. Therefore, the ability of PAMAM-Arg in transferring a luciferase gene to ovarian carcinoma SK-OV3 cells has been examined, and the cytotoxicity of the cationic polymer has been investigated. In addition, the suppression of cell proliferation has been evaluated by transferring an EGFR antisense gene to SK-OV3 cells using PAMAM-Arg. Polyethyleneimine (PEI) 25K was used as a positive control. Results: As a result, in vitro gene transfection efficiency of PAMAM-Arg was enhanced with increasing transfection time and NP ratios. PAMAM-Arg transferred the luciferase gene into cells more efficiently than PEI. In addition, PAMAM-Arg was minimally toxic to the cells whereas PEI 25K was highly toxic. The polyplexes formed by the EGFR antisense gene and PAMAM-Arg significantly reduced thymidine incorporation into the cells suggesting the suppression of cancer cell proliferation. Conclusion: These results suggest that a PAMAM-ArgEGFR antisense gene complex can be used as a safe and efficient therapeutic agent for cancer gene therapy.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalDrug Development and Industrial Pharmacy
Volume37
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Antisense gene
  • Cancer gene therapy
  • Epidermal growth factor receptor
  • L-arginine-grafted-polyamidoamine dendrimer
  • Polyethyleneimine
  • Thymidine incorporation

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