Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes

Shih Jiuan Chiu, Shujun Liu, Danilo Perrotti, Guido Marcucci, Robert J. Lee

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)


A novel transferrin receptor (TfR)-targeted liposomal formulation was synthesized and evaluated for the delivery of a phosphorothioate antisense oligodeoxyribonucleotide (ODN) (G3139, oblimerson sodium, or Genasense™) to Bcl-2 in K562 leukemia cells. Liposomes composed of DC-Chol/egg PC/PEG-DSPE (25:73.5:1.5, mol/mol/mol) were loaded with G3139 with high efficiency (70-80%). To prepare targeted liposomes, transferrin was first coupled to PEG-DSPE and then incorporated into the bilayer by post-insertion. The liposomes had a mean diameter of 100 to 150 nm and exhibited colloidal stability for up to 8 weeks. Uptake of Tf-conjugated G3139-containing liposomes in TfR positive K562 cells was found to be more efficient than that of the non-targeted control formulation and could be blocked by excess free Tf. Treatment with Tf-conjugated liposomes resulted in Bcl-2 protein downregulation in K562 cells that was approximately 2-fold greater than with non-targeted liposomes (p < 0.05) and 10-fold greater than with free G3139. Treatment with 2 μM G3139 in Tf-conjugated liposomes resulted in > 80% reduction in Bcl-2 transcript. In addition, Tf-conjugated liposomal G3139-sensitized K562 cells to daunorubicin, lowering IC50 from 1.8 μM to 0.18 μM. In conclusion, Tf-conjugated liposomes are effective delivery vehicles for G3139 antisense oligos in TfR positive K562 cells and warrant further investigation as an in vivo oligo delivery vehicle.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalJournal of Controlled Release
Issue number2
Publication statusPublished - May 15 2006


  • Antisense oligonucleotide
  • Bcl-2
  • Leukemia
  • Liposomes
  • Transferrin

ASJC Scopus subject areas

  • Pharmaceutical Science


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