Construction of a two-in-one liposomal system (TWOLips) for tumor-targeted combination therapy.
Construction of a two-in-one liposomal system (TWOLips) for tumor-targeted combination therapy.
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DOI：
10.1016/j.ijpharm.2014.09.055
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发表时间：
2014-12
影响因子：
5.8
通讯作者：
Tingting Su;Yingying Long;Chunyue Deng;Ling-lin Feng;Xiaoling Zhang;Zhang-bao Chen;Chong Li
中科院分区：
文献类型：
--
作者：
Tingting Su;Yingying Long;Chunyue Deng;Ling-lin Feng;Xiaoling Zhang;Zhang-bao Chen;Chong Li
在肿瘤学中，越来越需要更简单，更有选择性的方法来将药物治疗直接递送到肿瘤部位。对于组合疗法，多种药物的同时靶向递送将代表显著的改进。与以往采用新方法的工作不同，我们从两个单一载药脂质体构建了一种新型的二合一脂质体系统（TWOLips）。我们的研究结果表明，TWOLips可以通过一个简单的过程，通过二氧化硅涂层的一个脂质体和孵育的第二个脂质体。TWOLips的平均直径为100 nm，载药率相对较高（阿霉素为96.8% ± 0.9%，考布他汀为78.4% ± 1.2%），储存稳定性较高。TWOLips通过添加靶向部分（一种源自天然血管内皮生长因子的全氨基酸肽）进行修饰，导致在体外和体内与血管内皮生长因子受体2（一种肿瘤发生标记物）的强选择性结合。TWOLips显著抑制肿瘤生长和血管生成，并提高A375黑色素瘤异种移植小鼠的存活率。TWOLips系统的潜在毒性风险较低。由于逐步组装可以进一步进行（额外的载药脂质体），TWOLips显示出治疗许多癌症的潜力，特别是那些需要多种药物的癌症。
In oncology, there is a growing need for simpler, more selective methods to deliver drug therapies directly to the tumor site. For combination therapies, simultaneous targeted delivery of multiple drugs would represent a significant improvement. In contrast to previous work that took ade novoapproach, we constructed a novel two-in-one liposomal system (TWOLips) from two single drug-loaded liposomes. Our results demonstrated that TWOLips could be prepared by a simple process, through silica coating of one liposome and incubation with the second liposome. TWOLips had a mean diameter of 100 nm, relatively high drug loading rates (96.8% ± 0.9% for doxorubicin and 78.4% ± 1.2% for combretastatin), and high storage stability. TWOLips modification by adding a targeting moiety, an alld-amino acid peptide derived from a natural vascular endothelial growth factor, resulted in strong, selective binding to vascular endothelial growth factor receptor 2, a tumorigenesis marker,in vitroandin vivo. TWOLips significantly inhibited tumor growth and angiogenesis and enhanced survival in mice with A375 melanoma xenografts. The TWOLips system had a low potential risk of toxicity. Since the stepwise assembly could be carried further (additional drug-loaded liposomes), TWOLips shows potential as a treatment for many cancers, especially those that require multiple drugs.