Mizuguchi H, Nakanishi T, Nakanishi M, Nakagawa T, Nakagawa S, Mayumi T
Faculty of Pharmaceutical Science, Osaka University, Japan.
Cancer Lett. 1996 Feb 27;100(1-2):63-9. doi: 10.1016/0304-3835(95)04081-1.
Previously, we reported that experimental i.p. administration of fusogenic liposomes containing fragment A of diphtheria toxin (DTA) completely regressed ascites tumors without any severe side effects. In this study, we examined the therapeutic effects of intratumor injection of fusogenic liposomes using ddY mice implanted with Sarcoma-180 (S-180) cells intradermally. Intratumor injections of fusogenic liposomes containing DTA significantly inhibited the tumor growth as assessed by the relative mean tumor volume, and by the survival time of mice. No therapeutic effects were observed when simple liposomes containing DTA or empty fusogenic liposomes were administered. Using [3H]inulin encapsulated in fusogenic liposomes as a marker, we demonstrated that fusogenic liposomes delivered their contents into the solid tumor cells about 15 times more efficiently than simple liposomes. These results suggest that intratumor administration of fusogenic liposomes containing DTA is a highly effective approach to the local treatment of solid tumors.
此前,我们报道经腹腔注射含有白喉毒素A片段(DTA)的融合脂质体可使腹水肿瘤完全消退,且无任何严重副作用。在本研究中,我们使用经皮植入肉瘤180(S-180)细胞的ddY小鼠,检测了肿瘤内注射融合脂质体的治疗效果。通过相对平均肿瘤体积和小鼠存活时间评估,肿瘤内注射含DTA的融合脂质体可显著抑制肿瘤生长。当注射含DTA的单纯脂质体或空融合脂质体时,未观察到治疗效果。使用包裹在融合脂质体中的[3H]菊粉作为标记物,我们证明融合脂质体将其内容物递送至实体瘤细胞的效率比单纯脂质体高约15倍。这些结果表明,肿瘤内注射含DTA的融合脂质体是一种局部治疗实体瘤的高效方法。