Aptamer-mediated hollow MnO 2 for targeting the delivery of sorafenib

适体 索拉非尼 肝细胞癌 血清反应因子 材料科学 癌症研究 体内 化学 生物物理学 分子生物学 医学 生物化学 生物 转录因子 基因 生物技术
作者
Ziyue Wang,Cuicui Wu,J. Liu,Shunxin Hu,Junli Yu,Qiangqiamg Yin,Hongda Tian,Zhipeng Ding,Guiqiang Qi,Li Wang,Liguo Hao
出处
期刊:Drug Delivery [Informa]
卷期号:30 (1): 28-39 被引量:17
标识
DOI:10.1080/10717544.2022.2149897
摘要

Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.
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