Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery

Shinji Kakimoto, Tetsuji Moriyama, Toshizumi Tanabe, Seiji Shinkai, Takeshi Nagasaki

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

In order to enhance the internalization of exogenous gene and add cell specificity to non-viral vectors, receptor-binding elements have been widely utilized to mimic the virus infection. Herein, for the purpose of intensifying the effects of the ligand on gene delivery, dual receptor-binding elements, transferrin (Tf) and transforming growth factor alpha (TGFα), were introduced into the polyethyleneimine polyplex. The transfection and internalization efficiency by dual Tf- and TGFα-introduced polyplex (Tf&TGFα-polyplex) was examined in A549 and CHO-K1 cells, respectively. In A549, Tf&TGFα-polyplex had higher transfection efficiency when compared to that by single Tf- or TGFα-introduced polyplex (Tf-polyplex and TGFα-polyplex), respectively, while no enhancement was observed in CHO-K1. Moreover, in A549, the internalization efficiency of dual Tf&TGFα-polyplex was higher than that of single Tf- and TGFα-polyplex. In contrast, in CHO-K1, no difference in internalization efficiency was observed. In the presence of excess free transferrin or TGFα, the internalization efficiency of Tf&TGFα-polyplex was strongly inhibited only in A549, not in CHO-K1. In summary, the enhancement of internalization efficiency by dual ligands is an important factor for improving transfection efficiency. In addition, the effect of dual ligands depends on cell species; receptor-mediated and efficient internalization may be related to this enhanced transfection efficiency.

Original languageEnglish
Pages (from-to)242-249
Number of pages8
JournalJournal of Controlled Release
Volume120
Issue number3
DOIs
Publication statusPublished - Jul 31 2007

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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