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载姜黄素和考布他汀 A4 磷酸的肝靶向脂质体的制备、表征及抗肿瘤作用。

Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: preparation, characterization, and antitumor effects.

机构信息

School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, China,

School of Pharmacy, Weifang Medical University, Weifang, Shandong, China,

出版信息

Int J Nanomedicine. 2019 Mar 8;14:1789-1804. doi: 10.2147/IJN.S188971. eCollection 2019.

DOI:10.2147/IJN.S188971
PMID:30880980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6413741/
Abstract

BACKGROUND

Recent efforts have been focused on combining two or more therapeutic approaches with different mechanisms to enhance antitumor therapy. Moreover, nanosize drug-delivery systems for codelivering two drugs with proapoptotic and antiangiogenic activities have exhibited great potential in efficient treatment of cancers.

METHODS

Glycyrrhetinic acid (GA)-modified liposomes (GA LPs) for liver-targeted codelivery of curcumin (Cur) and combretastatin A4 phosphate (CA4P) were prepared and characterized. In vitro cellular uptake, cytotoxicity, cell migration, in vivo biodistribution, antitumor activity, and histopathological studies were performed.

RESULTS

Compared with unmodified LPs (Cur-CA4P LPs), Cur-CA4P/GA LPs were taken up effectively by human hepatocellular carcinoma cells (BEL-7402) and showed higher cytotoxicity than free drugs. In vivo real-time near-infrared fluorescence-imaging results indicated that GA-targeted LPs increased accumulation in the tumor region. Moreover, Cur-CA4P/GA LPs showed stronger inhibition of tumor proliferation than Cur, Cur + CA4P, and Cur-CA4P LPs in vivo antitumor studies, which was also verified by H&E staining.

CONCLUSION

GA-modified LPs can serve as a promising nanocarrier for liver-targeted co-delivery of antitumor drugs against hepatocellular carcinoma.

摘要

背景

最近的研究重点集中在结合两种或多种具有不同机制的治疗方法上，以增强抗肿瘤治疗效果。此外，具有促凋亡和抗血管生成作用的两种药物共递送的纳米药物递送系统在有效治疗癌症方面显示出巨大潜力。

方法

制备并表征了甘草次酸（GA）修饰的脂质体（GA LPs），用于姜黄素（Cur）和考布他汀 A4 磷酸酯（CA4P）的肝靶向共递药。进行了细胞摄取、细胞毒性、细胞迁移、体内生物分布、抗肿瘤活性和组织病理学研究。

结果

与未修饰的脂质体（Cur-CA4P LPs）相比，Cur-CA4P/GA LPs 被人肝癌细胞（BEL-7402）有效摄取，并显示出比游离药物更高的细胞毒性。体内实时近红外荧光成像结果表明，GA 靶向脂质体增加了肿瘤区域的积累。此外，Cur-CA4P/GA LPs 在体内抗肿瘤研究中比 Cur、Cur+CA4P 和 Cur-CA4P LPs 表现出更强的抑制肿瘤增殖作用，这也通过 H&E 染色得到了验证。

结论

GA 修饰的脂质体可作为一种有前途的纳米载体，用于肝靶向共递抗肝癌的抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/14510fdae1fa/ijn-14-1789Fig13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/e54b5d69fdf2/ijn-14-1789Fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/ad24d7fff107/ijn-14-1789Fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/14510fdae1fa/ijn-14-1789Fig13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/e54b5d69fdf2/ijn-14-1789Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/a76ecdaa1206/ijn-14-1789Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/869866ba39be/ijn-14-1789Fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/a7c4f41b8173/ijn-14-1789Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/6e0dd7c98da2/ijn-14-1789Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/88e6070a5927/ijn-14-1789Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/b8592b28cdd7/ijn-14-1789Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/ba39da44dd39/ijn-14-1789Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/9ee5a0459017/ijn-14-1789Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/51e0b306ed75/ijn-14-1789Fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/ad24d7fff107/ijn-14-1789Fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ad/6413741/14510fdae1fa/ijn-14-1789Fig13.jpg

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