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透明质酸修饰的柔红霉素联合和厚朴酚阳离子脂质体治疗乳腺癌并消除血管生成拟态通道。

Hyaluronic acid modified daunorubicin plus honokiol cationic liposomes for the treatment of breast cancer along with the elimination vasculogenic mimicry channels.

机构信息

a Department of Pharmaceutical Engineering , Beijing Institute of Petrochemical Technology , Beijing , China.

b School of Pharmacy , Liaoning University of Traditional Chinese Medicine , Dalian , China.

出版信息

J Drug Target. 2018 Nov;26(9):793-805. doi: 10.1080/1061186X.2018.1428809. Epub 2018 Jan 24.

DOI:10.1080/1061186X.2018.1428809
PMID:29334266
Abstract

BACKGROUND

Breast cancer is an alarming global public health problem and a main cause of cancer-related death in women. Systemic chemotherapy is the most widely used treatment for breast cancer. However, current chemotherapy treatments are far from desirable due to poor targeting specificity, severe side effects and vasculogenic mimicry (VM).

PURPOSE

Hyaluronic acid (HA)-modified daunorubicin plus honokiol (HNK) cationic liposomes were prepared and characterised for treatment of breast cancer by eliminating VM.

METHODS

HA-modified daunorubicin plus HNK cationic liposomes were prepared by a thin-film hydration method. Evaluations were performed on MCF-7 cells and MDA-MB-435S cells, which are human breast cancer cells, and xenografts of MDA-MB-435S cells.

RESULTS

In vitro results revealed that the HA-modified daunorubicin plus HNK cationic liposomes enhanced the cellular uptake and destroyed VM channels. In vivo results demonstrated that the liposomes prolonged the circulation time in the blood, obviously accumulated in the tumour region, and enhanced the overall anticancer effects. Action mechanisms were related to down-regulation of VM protein indicators including FAK, EphA2, MMP-2 and MMP-9.

CONCLUSIONS

The prepared HA-modified daunorubicin plus HNK cationic liposomes may serve as a promising therapeutic strategy for the treatment of breast cancer.

摘要

背景

乳腺癌是一个令人震惊的全球公共卫生问题,也是女性癌症相关死亡的主要原因。系统化疗是乳腺癌最广泛使用的治疗方法。然而,由于靶向特异性差、副作用严重和血管生成拟态(VM)的存在,目前的化疗治疗远非理想。

目的

本研究旨在通过消除 VM 来制备透明质酸(HA)修饰的柔红霉素加和厚朴酚(HNK)阳离子脂质体治疗乳腺癌。

方法

采用薄膜水化法制备 HA 修饰的柔红霉素加 HNK 阳离子脂质体。在 MCF-7 细胞和 MDA-MB-435S 细胞(人乳腺癌细胞)及其 MDA-MB-435S 细胞的异种移植瘤上进行评估。

结果

体外实验结果表明,HA 修饰的柔红霉素加 HNK 阳离子脂质体增强了细胞摄取并破坏了 VM 通道。体内实验结果表明,脂质体延长了血液中的循环时间,明显聚集在肿瘤区域,并增强了整体抗癌作用。作用机制与下调 FAK、EphA2、MMP-2 和 MMP-9 等 VM 蛋白标志物有关。

结论

所制备的 HA 修饰的柔红霉素加 HNK 阳离子脂质体可能成为治疗乳腺癌的一种有前途的治疗策略。

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