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

doi:10.1016/j.nano.2015.04.006

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

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article

28 Citations (Scopus)

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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 language	English
Pages (from-to)	1445-1454
Number of pages	10
Journal	Nanomedicine: Nanotechnology, Biology and Medicine
Volume	11
Early online date	28 Apr 2015
DOIs	https://doi.org/10.1016/j.nano.2015.04.006
Publication status	Published - Aug 2015

Keywords

cancer therapy
gene delivery
endrimer
lactoferricin
lactoferrin

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Profiles

Christine Dufès

c.dufes@strath.ac.uk

Strathclyde Institute Of Pharmacy And Biomedical Sciences - Reader

Person: Academic

Projects

1 Finished

Development of tumour-targeted gene delivery systems for intravenous cancer therapy

Dufès, C.

MRC (Medical Research Council)

1/06/12 → 31/05/15

Project: Research

Cite this

Lim, L. Y., Koh, P. Y., Somani, S., Al Robaian, M., Karim, R., Yean, Y. L., Mitchell, J., Tate, R. J., Edrada-Ebel, R., Blatchford, D. R., Mullin, M., & Dufès, C. (2015). Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes. Nanomedicine: Nanotechnology, Biology and Medicine, 11, 1445-1454. https://doi.org/10.1016/j.nano.2015.04.006

Lim, Li Ying ; Koh, Pei Yin ; Somani, Sukrut ; Al Robaian, Majed ; Karim, Reatul ; Yean, Yi Lyn ; Mitchell, Jennifer ; Tate, Rothwelle J. ; Edrada-Ebel, RuAngelie ; Blatchford, David R. ; Mullin, Margaret ; Dufès, Christine. / Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes. In: Nanomedicine: Nanotechnology, Biology and Medicine. 2015 ; Vol. 11. pp. 1445-1454.

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title = "Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes",

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.",

keywords = "cancer therapy, gene delivery, endrimer, lactoferricin, lactoferrin",

author = "Lim, {Li Ying} and Koh, {Pei Yin} and Sukrut Somani and {Al Robaian}, Majed and Reatul Karim and Yean, {Yi Lyn} and Jennifer Mitchell and Tate, {Rothwelle J.} and RuAngelie Edrada-Ebel and Blatchford, {David R.} and Margaret Mullin and Christine Duf{\`e}s",

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Lim, LY, Koh, PY, Somani, S, Al Robaian, M, Karim, R, Yean, YL, Mitchell, J, Tate, RJ , Edrada-Ebel, R, Blatchford, DR, Mullin, M & Dufès, C 2015, 'Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes', Nanomedicine: Nanotechnology, Biology and Medicine, vol. 11, pp. 1445-1454. https://doi.org/10.1016/j.nano.2015.04.006

Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes. / Lim, Li Ying; Koh, Pei Yin; Somani, Sukrut; Al Robaian, Majed; Karim, Reatul; Yean, Yi Lyn; Mitchell, Jennifer; Tate, Rothwelle J.; Edrada-Ebel, RuAngelie; Blatchford, David R.; Mullin, Margaret; Dufès, Christine.

In: Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 11, 08.2015, p. 1445-1454.

Research output: Contribution to journal › Article

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AU - Lim, Li Ying

AU - Koh, Pei Yin

AU - Somani, Sukrut

AU - Al Robaian, Majed

AU - Karim, Reatul

AU - Yean, Yi Lyn

AU - Mitchell, Jennifer

AU - Tate, Rothwelle J.

AU - Edrada-Ebel, RuAngelie

AU - Blatchford, David R.

AU - Mullin, Margaret

AU - Dufès, Christine

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N2 - 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.

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M3 - Article

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SN - 1549-9634

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