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多壁碳纳米管共递送索拉非尼和表皮生长因子受体 siRNA 增强肝癌的肿瘤抑制作用。

Multiwalled carbon nanotubes co-delivering sorafenib and epidermal growth factor receptor siRNA enhanced tumor-suppressing effect on liver cancer.

机构信息

Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.

出版信息

Aging (Albany NY). 2021 Jan 13;13(2):1872-1882. doi: 10.18632/aging.103905.

Abstract

OBJECTIVE

This study aimed to investigate the effects of multiwalled carbon nanotubes (MWNTs) co-delivering sorafenib (Sor) and epidermal growth factor receptor (EGFR) siRNA (MWNT/Sor/siRNA) on tumor growth in liver cancer (LC).

RESULTS

MWNT/Sor/siRNA was proved to possess increased Sor release, high siRNA stability, and enhanced cellular uptake. In addition, MWNT treatment has few effects on cell proliferation and apoptosis in HepG2 cells; however, MWNT/Sor/siRNA treatment significantly inhibited clone number and induced cell apoptosis, which shows a more favorable antitumor effect than MWNT/Sor and free Sor and free siRNA in HepG2 cells. Moreover MWNT/Sor/siRNA treatment has the most significant antitumor effect .

CONCLUSIONS

MWNT/Sor/siRNA exhibited a superior antitumor effect and .

METHODS

The MWNT/Sor and MWNT/Sor/siRNA were prepared, and then the morphologies of MWNT/Sor/siRNA were analyzed. Sor release assay, siRNA stability and cellular uptake of MWNT/Sor/siRNA were performed as well. Next, the effects of MWNT, free Sor, free siRNA, MWNT/Sor and MWNT/Sor/siRNA were evaluated by colony-forming assay, and cell apoptosis assay in HepG2 cells. Meanwhile, the level of EGFR and proteins associated with apoptosis was tested. Furthermore, the anti-tumor effects of MWNT/Sor/siRNA on LC xenograft mice were also unraveled.

摘要

目的

本研究旨在探讨多壁碳纳米管(MWNTs)共递送索拉非尼(Sor)和表皮生长因子受体(EGFR)siRNA(MWNT/Sor/siRNA)对肝癌(LC)肿瘤生长的影响。

结果

MWNT/Sor/siRNA 被证明具有增加的 Sor 释放、高 siRNA 稳定性和增强的细胞摄取。此外,MWNT 处理对 HepG2 细胞的增殖和细胞凋亡几乎没有影响;然而,MWNT/Sor/siRNA 处理显著抑制克隆数并诱导细胞凋亡,这表明与 MWNT/Sor 和游离 Sor 和游离 siRNA 相比,MWNT/Sor/siRNA 在 HepG2 细胞中具有更有利的抗肿瘤作用。此外,MWNT/Sor/siRNA 治疗具有最显著的抗肿瘤作用。

结论

MWNT/Sor/siRNA 表现出优越的抗肿瘤作用。

方法

制备 MWNT/Sor 和 MWNT/Sor/siRNA,并分析 MWNT/Sor/siRNA 的形态。进行 Sor 释放测定、siRNA 稳定性和 MWNT/Sor/siRNA 的细胞摄取。接下来,通过集落形成测定和 HepG2 细胞中的细胞凋亡测定评估 MWNT、游离 Sor、游离 siRNA、MWNT/Sor 和 MWNT/Sor/siRNA 的作用。同时,检测 EGFR 水平和与凋亡相关的蛋白。此外,还揭示了 MWNT/Sor/siRNA 对 LC 异种移植小鼠的抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/7880368/6fd6bda57097/aging-13-103905-g001.jpg

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