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乳铁蛋白修饰蛋白纳米球增强了肝细胞癌的口服 COX-2 抑制剂/草药疗法。

Decorating protein nanospheres with lactoferrin enhances oral COX-2 inhibitor/herbal therapy of hepatocellular carcinoma.

机构信息

Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.

Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.

出版信息

Nanomedicine (Lond). 2018 Oct;13(19):2377-2395. doi: 10.2217/nnm-2018-0134. Epub 2018 Oct 22.

Abstract

AIM

Lactoferrin (LF)-targeted gliadin nanoparticles (GL-NPs) were developed for targeted oral therapy of hepatocellular carcinoma.

MATERIALS & METHODS: Celecoxib and diosmin were incorporated in the hydrophobic matrix of GL-NPs whose surface was decorated with LF by electrostatic interaction for binding to asialoglycoprotein receptors overexpressed by liver cancer cells.

RESULTS

Targeted GL-NPs showed enhanced cytotoxic activity and increased cellular uptake in liver tumor cells compared with nontargeted NPs. Moreover, they demonstrated superior in vivo antitumor effects including reduction in the expression levels of tumor biomarkers and induction of caspase-mediated apoptosis. Ex vivo imaging of isolated organs exhibited extensive accumulation of NPs in livers more than other organs.

CONCLUSION

LF-targeted GL-NPs could be considered as an efficient nanoplatform for targeted oral drug delivery for liver cancer therapy.

摘要

目的

乳铁蛋白(LF)靶向麦胶纳米粒(GL-NPs)被开发用于肝细胞癌的靶向口服治疗。

材料与方法

塞来昔布和地奥司明被包载于 GL-NPs 的疏水性基质中,GL-NPs 的表面通过静电相互作用被 LF 修饰,以与肝癌细胞过度表达的去唾液酸糖蛋白受体结合。

结果

与非靶向 NP 相比,靶向 GL-NPs 显示出增强的细胞毒性活性和增加的肝癌细胞摄取。此外,它们表现出优越的体内抗肿瘤作用,包括降低肿瘤标志物的表达水平和诱导半胱天冬酶介导的细胞凋亡。离体器官的体外成像显示,NP 在肝脏中的积累明显多于其他器官。

结论

LF 靶向 GL-NPs 可被视为用于肝癌治疗的靶向口服药物递送的有效纳米平台。

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