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


BACKGROUND
Specific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Li Ying
LY
Lim
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Pei Yin
PY
Koh
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Sukrut
S
Somani
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Majed
M
Al Robaian
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Reatul
R
Karim
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Yi Lyn
YL
Yean
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Jennifer
J
Mitchell
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Rothwelle J
RJ
Tate
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
RuAngelie
R
Edrada-Ebel
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
David R
DR
Blatchford
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Margaret
M
Mullin
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom. Electronic address: C.Dufes@strath.ac.uk.
Christine
C
Dufès
D061605:Administration, Intravenous; D000818:Animals; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000008:administration & dosage*; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy*
D050091:Dendrimers; C082171:lactoferricin B; D007781:Lactoferrin
Cancer therapy; Dendrimer; Gene delivery; Lactoferricin; Lactoferrin