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载载蛋白纳米粒包裹的 AFP siRNA 可诱导人肝癌细胞凋亡并增强阿霉素的细胞毒性作用。

PLGA nanoparticles containing α-fetoprotein siRNA induce apoptosis and enhance the cytotoxic effects of doxorubicin in human liver cancer cell line.

机构信息

Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.

Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand; Research Network NANOTEC-MU in Theranostic Nanomedicine, Thailand.

出版信息

Biochem Biophys Res Commun. 2021 May 14;553:191-197. doi: 10.1016/j.bbrc.2021.03.086. Epub 2021 Mar 26.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers and is a leading cause of death. Delivery of therapeutic molecules, e.g., siRNA, to HCC cells could potentially be an alternative treatment for HCC. In this study, the siRNA targeting α-fetoprotein (AFP) mRNA was found to specifically induce apoptosis and significant cell death in HepG2 cells. It also enhanced the cytotoxic effects of doxorubicin by about two-fold, making it the candidate therapeutic molecule for HCC treatment. To deliver the siRNAs into HCC cells, the AFP siRNAs were loaded into the nanoparticles based on poly (lactic-co-glycolic) acid (PLGA). These nanoparticles induced apoptosis in HepG2 cells and synergistically increased the cytotoxicity of doxorubicin. In summary, the delivery of the AFP siRNA-loaded PLGA nanoparticles in combination with doxorubicin could be a very promising approach for the treatment of HCC.

摘要

肝细胞癌 (HCC) 是最常见的癌症之一,也是死亡的主要原因。将治疗分子,例如 siRNA,递送到 HCC 细胞中可能是 HCC 的一种替代治疗方法。在这项研究中,靶向甲胎蛋白 (AFP) mRNA 的 siRNA 被发现能够特异性诱导 HepG2 细胞凋亡和显著细胞死亡。它还使多柔比星的细胞毒性作用提高了约两倍,使其成为 HCC 治疗的候选治疗分子。为了将 siRNA 递送到 HCC 细胞中,将 AFP siRNA 装载到基于聚 (乳酸-共-乙醇酸) (PLGA) 的纳米颗粒中。这些纳米颗粒诱导 HepG2 细胞凋亡,并协同增加多柔比星的细胞毒性。总之,载有 AFP siRNA 的 PLGA 纳米颗粒与多柔比星联合递送可能是治疗 HCC 的一种很有前途的方法。

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