Application of fusogenic liposomes containing fragment A of diphtheria toxin to cancer therapy.

H Mizuguchi,M Nakanishi,T Nakanishi,S Nakagawa,T Nakagawa,T Mayumi

doi:10.1038/bjc.1996.83

H Mizuguchi, M Nakanishi + Show 4 more

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https://doi.org/10.1038/bjc.1996.83

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Abstract

Previously we reported that fusogenic liposomes, prepared by fusing simple liposomes with Sendai virus particles, could introduce their contents directly and efficiently into the cytoplasm. In this study, we examined the anti-tumour activity of fusogenic liposomes containing fragment A of diphtheria toxin (DTA). Fusogenic liposomes containing DTA showed high cytotoxicity against sarcoma-180 (S-180) cells in vitro. When these liposomes were administered into the abdominal cavity of ddY mice carrying S-180, tumour cells completely disappeared in four of six tumour-bearing mice without decrease in body weight. Neither simple liposomes containing DTA nor empty fusogenic liposomes had any effect on tumour suppression. We conclude that fusogenic liposomes containing DTA are new and potentially effective tools for the treatment of ascites tumours without any severe side-effects.

Highlights

We reported that our fusogenic liposomes fused with cell membrane using the mechanism of infection by Sendai virus, and that fusogenic liposomes containing diphtheria toxin (DTA) killed mouse L cells and human HeLa cells quite efficiently (Uchida et al, 1979; Nakanishi et al, 1985, 1995, M Nakanishi et al, manuscript in preparation)
Because Sendai virus can infect a wide variety of cells with sialic acid, a common component of glycolipid and glycoprotein, as receptors, the fusogenic liposomes containing DTA may kill a variety of cells, including tumorigenic cells or suspension cells
Neither simple liposomes containing DTA nor empty fusogenic liposomes had any influence on the viability of S-180 cells (Figure 1)

Summary

Methods

Egg phosphatidylcholine (PC) and L-a-dimyristoryl phosphatidic acid (PA) were obtained from Nippon Oil & Fats, Tokyo, Japan. Cholesterol (Chol) was obtained from Sigma, St Louis, MO, USA. Nuclepore) was obtained from Costar, Cambridge, MA, USA. Male ddY mice were obtained from Shimizu Experimental Animal Co, Kyoto, Japan. DTA was prepared as described previously (Uchida et al, 1979) with modification using hydophobic chomatography and ion exchange chromatography (M Nakanishi et al, manuscript in preparation). Cytotoxicity of DTA was examined by using toxin-sensitive Vero cells. We found that DTA prepared by us was not toxic to the cells even when it was added in cultured medium at 100 jig ml-' for 24 h (M Nakanishi et al, manuscript in preparation)

Results

Discussion

Conclusion