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脂质体共递送多西他赛和白藜芦醇协同增强抗前列腺癌活性。

Co-delivery of Docetaxel and Resveratrol by liposomes synergistically boosts antitumor efficiency against prostate cancer.

机构信息

Institute of Medical Sciences, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, PR China.

Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266555, PR China.

出版信息

Eur J Pharm Sci. 2022 Jul 1;174:106199. doi: 10.1016/j.ejps.2022.106199. Epub 2022 May 6.

Abstract

Combination therapy is frequently used in cancer treatments. Delivery of combined anticancer agents loaded in a nanocarrier would be a promising option for combination therapy. Here, we designed PEGylated nano-liposomes for co-delivery Docetaxel (Doc) and Resveratrol (Res) to evaluate antitumor efficiency of the combined drugs in prostate cancer. The average diameter of the liposomes was 99.67 nm with a spheral-like shape. Drug release studies showed that both drugs could synchronously leak from the liposomes in a sustained release behavior. Cellular uptake results demonstrated that liposomes could effectively deliver more cargos into cells than other formulations. Moreover, co-loaded liposomes with Doc/Res in a molar ratio of 1:2 exhibited significantly higher cytotoxicity than a mixed solution containing both drugs on cancer cells. In the study of caspase 3, we found that the combination of Doc and Res could significantly increase the activity of caspase 3 enzyme compared with Doc alone. Animal studies revealed that co-encapsulated Doc/Res in liposomes predominantly inhibited tumor growth in PC3 bearing Balb/c nude mice, as evidenced by a change in cell proliferation and apoptosis parameters. Importantly, little toxicities and prolonged survival time were observed in mice treated with liposome-loaded Doc/Res than control group exposed to liposome-free Doc/Res. These results provided evidence that loading of Doc/Res in a nano-liposome is an efficient delivery formulation for synergistic treating prostate cancer.

摘要

联合治疗经常用于癌症治疗。将联合抗癌药物装载在纳米载体中进行递送,将是联合治疗的一种有前途的选择。在这里,我们设计了聚乙二醇化的纳米脂质体来共递送多西他赛(Doc)和白藜芦醇(Res),以评估联合药物在前列腺癌中的抗肿瘤效率。脂质体的平均直径为 99.67nm,呈球形。药物释放研究表明,两种药物可以以持续释放的方式同步从脂质体中泄漏。细胞摄取结果表明,与其他制剂相比,脂质体可以更有效地将更多的药物输送到细胞中。此外,以 1:2 的摩尔比共载有 Doc/Res 的脂质体在癌细胞上表现出比含有两种药物的混合溶液更高的细胞毒性。在 caspase 3 的研究中,我们发现 Doc 和 Res 的联合使用可以显著增加 caspase 3 酶的活性,与单独使用 Doc 相比。动物研究表明,载有 Doc/Res 的脂质体主要抑制了携带 PC3 的 Balb/c 裸鼠中的肿瘤生长,这表现在细胞增殖和凋亡参数的变化。重要的是,与对照组相比,接受载有 Doc/Res 的脂质体治疗的小鼠毒性较小,存活时间延长。这些结果为 Doc/Res 装载在纳米脂质体中是协同治疗前列腺癌的有效递送制剂提供了证据。

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