Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes

Li Ying Lim, Pei Yin Koh, Sukrut Somani, Majed Al Robaian, Reatul Karim, Yi Lyn Yean, Jennifer Mitchell, Rothwelle J. Tate, RuAngelie Edrada-Ebel, David R. Blatchford, Margaret Mullin, Christine Dufès

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Abstract

The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy.
The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy.
Original languageEnglish
Pages (from-to)1445-1454
Number of pages10
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume11
Early online date28 Apr 2015
DOIs
Publication statusPublished - Aug 2015

Keywords

  • cancer therapy
  • gene delivery
  • endrimer
  • lactoferricin
  • lactoferrin

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