The combined effect of encapsulating curcumin and C6 ceramide in liposomal nanoparticles against osteosarcoma.

The combined effect of encapsulating curcumin and C6 ceramide in liposomal nanoparticles against osteosarcoma.
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DOI:
10.1021/mp400366r
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发表时间:
2014-02-03
影响因子:
4.9
通讯作者:
Pochampally R
Pochampally R
中科院分区:
医学2区
文献类型:
--
作者:
Dhule SS;Penfornis P;He J;Harris MR;Terry T;John V;Pochampally R

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本研究探讨了姜黄素和C6神经酰胺(C6)对骨肉瘤(OS)细胞系的抗肿瘤潜力时,都封装在双层脂质体纳米粒子。制备三种脂质体制剂-姜黄素脂质体、C6脂质体和C6-姜黄素脂质体。与单独的姜黄素脂质体相比,姜黄素与C6组合在MG-63和KHOS OS细胞系的情况下显示出1.5倍增强的细胞毒性作用。重要的是,发现C6-姜黄素脂质体与OS细胞系相比对未转化的人细胞(人间充质干细胞)的毒性较小。此外,对KHOS细胞系的细胞周期测定显示,姜黄素脂质体通过上调细胞周期蛋白B1诱导G2/M期阻滞,而C6脂质体通过下调细胞周期蛋白D1诱导G1期阻滞。C6-姜黄素脂质体诱导G2/M期阻滞,并表现出细胞周期蛋白D1和细胞周期蛋白B1的表达水平的联合作用。使用人骨肉瘤异种移植物测定在体内测试制剂的效率。使用聚乙二醇化脂质体来增加血浆半衰期并用叶酸(FA)标记用于体内靶向递送,用C6-姜黄素-FA脂质体观察到肿瘤大小的显著减小。两种水不溶性药物姜黄素和C6在脂质体的脂质双层中的包封增强了细胞毒性作用,并验证了联合药物治疗的潜力。
This study examines the anti-tumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared – curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested in vivo using a human osteosarcoma xenograft assays. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy.
在连续和脉冲给药策略期间对靶向抗癌疗法的抵抗力的演变。
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