Surface modification of pharmaceutical nanocarriers with ascorbate residues improves their tumor-cell association and killing and the cytotoxic action of encapsulated paclitaxel in vitro
Surface modification of pharmaceutical nanocarriers with ascorbate residues improves their tumor-cell association and killing and the cytotoxic action of encapsulated paclitaxel in vitro
复制标题
DOI：
10.1007/s11095-008-9674-4
复制
发表时间：
2008-11-01
影响因子：
3.7
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
--
作者：
D'Souza, Gerard G. M.;Wang, Tao;Torchilin, Vladimir P.
目的。评价抗坏血酸作为一种新型配体在制备具有增强的肿瘤细胞特异性结合和细胞毒性的药物纳米载体方面的潜力。棕榈酰抗坏血酸以不同浓度被掺入脂质体中。根据尺寸和Zeta电位测量，选择了稳定的配方。肿瘤细胞与表达绿色荧光蛋白的非肿瘤细胞共培养，以确定棕榈酰抗坏血酸脂质体结合的特异性。脂质体被荧光标记，以便于通过流式细胞仪和荧光显微镜进行分析。用标准代谢试验检测棕榈酸酯抗坏血酸脂质体对多种细胞类型的细胞毒作用。实验还测定了低剂量紫杉醇与棕榈酸酯抗坏血酸脂质体结合后对不同细胞株的细胞毒作用。在共培养模型中，与非癌细胞相比，棕榈酸酯抗坏血酸脂质体优先与各种癌细胞结合。棕榈酸酯抗坏血酸脂质体在多种肿瘤细胞系中表现出抗癌毒性。此外，与普通脂质体相比，抗坏血酸脂质体提高了紫杉醇胶囊的有效性。结论。用抗坏血酸残基对脂质体进行表面修饰是一种靶向和杀伤某些类型肿瘤细胞的新方法，此外还可以增强脂质体传递紫杉醇的效果。
Purpose. To evaluate the potential of ascorbate as a novel ligand in the preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific binding and cytotoxicity.Methods. Palmitoyl ascorbate was incorporated into liposomes at varying concentrations. A stable formulation was selected based on size and zeta potential measurements. A co-culture of cancer cells with GFP expressing non-cancer cells was used to determine the specificity of palmitoyl ascorbate liposome binding. Liposomes were fluorescently labeled to facilitate analysis by flow cytometry and fluorescence microscopy. The cytotoxic action of palmitoyl ascorbate liposomes against a variety of cell types was assayed using a standard metabolic assay. The cytotoxic effect of a low dose of paclitaxel incorporated in palmitoyl ascorbate liposomes on various cell lines was also determined.Results. Palmitoyl ascorbate liposomes associated preferentially with various cancer cells compared to non-cancer cells in a co-culture model. Palmitoyl ascorbate liposomes exhibited anti-cancer toxicity in numerous cancer cell lines. Furthermore, ascorbate liposomes enhanced the effectiveness of encapsulated paclitaxel compared to paclitaxel encapsulated in 'plain' liposomes. Conclusions. Surface modification of liposomes with ascorbate residues represents a novel way to target and kill certain types of tumor cells and additionally can potentiate the effect of paclitaxel delivered by the liposomes.