核仁蛋白识别二氧化硅纳米粒子,通过激活Bax / Bcl-2 / caspase-3信号通路,诱导肝癌细胞凋亡,抑制细胞增殖。
Nucleolin recognizing silica nanoparticles inhibit cell proliferation by activating the Bax/Bcl-2/caspase-3 signalling pathway to induce apoptosis in liver cancer.
发表日期:2023
作者:
Liangliang Xiang, Yun Li, Xinyu Gu, Shujie Li, Junwei Li, Jinlong Li, Yongxiang Yi
来源:
Frontiers in Pharmacology
摘要:
多功能纳米载体平台展示了对于肝癌的诊断和治疗具有巨大的潜力。在这里,建立了一种新型的核糖核酸结合核蛋白响应性纳米粒子平台,用于核糖核酸结合核蛋白的同时检测和治疗肝癌。将AS1411适配体、淫羊藿素(ICT)和FITC纳入到介孔硅纳米颗粒中,标记为Atp-MSN (ICT@FITC) NPs,这是提供功能性的关键。目标核糖核酸结合核蛋白和AS1411适配体的特定组合导致AS1411从介孔硅纳米颗粒表面分离出来,使得FITC和ICT被释放。随后,可以通过监测荧光强度来检测核糖核酸结合核蛋白。此外,Atp-MSN (ICT@FITC) NPs不仅能抑制细胞增殖,还能提高ROS水平,并激活Bax/Bcl-2/caspase-3信号通路,在体内外诱导细胞凋亡。此外,我们的结果表明,Atp-MSN (ICT@FITC) NPs毒性低,并能诱导CD3+ T细胞浸润。因此,Atp-MSN (ICT@FITC) NPs可以提供一种可靠且安全的平台,用于同时鉴定和治疗肝癌。版权所有 © 2023 Xiang, Li, Gu, Li, Li, Li和Yi。
Multifunctional nanocarrier platforms have shown great potential for the diagnosis and treatment of liver cancer. Here, a novel nucleolin-responsive nanoparticle platform was constructed for the concurrent detection of nucleolin and treatment of liver cancer. The incorporation of AS1411 aptamer, icaritin (ICT) and FITC into mesoporous silica nanoparticles, labelled as Atp-MSN (ICT@FITC) NPs, was the key to offer functionalities. The specific combination of the target nucleolin and AS1411 aptamer caused AS1411 to separate from mesoporous silica nanoparticles surface, allowing FITC and ICT to be released. Subsequently, nucleolin could be detected by monitoring the fluorescence intensity. In addition, Atp-MSN (ICT@FITC) NPs can not only inhibit cell proliferation but also improve the level of ROS while activating the Bax/Bcl-2/caspase-3 signalling pathway to induce apoptosis in vitro and in vivo. Moreover, our results demonstrated that Atp-MSN (ICT@FITC) NPs had low toxicity and could induce CD3+ T-cell infiltration. As a result, Atp-MSN (ICT@FITC) NPs may provide a reliable and secure platform for the simultaneous identification and treatment of liver cancer.Copyright © 2023 Xiang, Li, Gu, Li, Li, Li and Yi.