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

Lim, Li Ying and Koh, Pei Yin and Somani, Sukrut and Al Robaian, Majed and Karim, Reatul and Yean, Yi Lyn and Mitchell, Jennifer and Tate, Rothwelle J. and Edrada-Ebel, RuAngelie and Blatchford, David R. and Mullin, Margaret and Dufès, Christine (2015) Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes. Nanomedicine: Nanotechnology, Biology and Medicine, 11 (6). pp. 1445-1454. ISSN 1549-9634 (https://doi.org/10.1016/j.nano.2015.04.006)

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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.