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在横纹肌肉瘤小鼠模型中,脂质体长春新碱的循环时间延长且肿瘤蓄积增加。

Prolonged circulation and increased tumor accumulation of liposomal vincristine in a mouse model of rhabdomyosarcoma.

作者信息

Roveri Maurizio, Pfohl Alice, Jaaks Patricia, Alijaj Nagjie, Leroux Jean-Christophe, Luciani Paola, Bernasconi Michele

机构信息

Experimental Infectious Diseases & Cancer Research, University Children's Hospital Zurich, 8008 Zurich, Switzerland.

Children's Research Center, University Children's Hospital Zurich, 8032 Zurich, Switzerland.

出版信息

Nanomedicine (Lond). 2017 May;12(10):1135-1151. doi: 10.2217/nnm-2017-0430. Epub 2017 Apr 27.

Abstract

AIM

Our goal was to improve vincristine (VCR) based rhabdomyosarcoma (RMS) therapy by encapsulating the drug into liposomes. A targeting strategy was attempted to enhance tumor accumulation.

MATERIALS & METHODS: VCR was loaded in control and peptide-decorated liposomes via an active method. The interaction of an RMS-specific peptide with the presumed target furin and the cellular uptake of both liposomal groups were studied in vitro. Pharmacokinetics and biodistribution of VCR-containing liposomes were assessed in an RMS xenograft mouse model.

RESULTS

Liposomes ensured high VCR concentration in plasma and in the tumor. Peptide-decorated liposomes showed modest uptake in RMS cells.

CONCLUSION

The investigated peptide-modified liposomal formulation may not be optimal for furin-mediated RMS targeting. Nevertheless, VCR-loaded liposomes could serve as a delivery platform for experimental RMS.

摘要

目的

我们的目标是通过将长春新碱(VCR)包裹在脂质体中来改进基于VCR的横纹肌肉瘤(RMS)治疗方法。尝试采用一种靶向策略来增强肿瘤蓄积。

材料与方法

通过主动载药法将VCR载入对照脂质体和肽修饰脂质体中。在体外研究了一种RMS特异性肽与假定靶点弗林蛋白酶的相互作用以及两种脂质体组的细胞摄取情况。在RMS异种移植小鼠模型中评估了含VCR脂质体的药代动力学和生物分布。

结果

脂质体确保了血浆和肿瘤中VCR的高浓度。肽修饰脂质体在RMS细胞中的摄取量适中。

结论

所研究的肽修饰脂质体制剂可能并非弗林蛋白酶介导的RMS靶向的最佳选择。尽管如此,载有VCR的脂质体可作为实验性RMS的递送平台。

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