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载有索拉非尼和阿霉素的低密度脂蛋白修饰的硅纳米颗粒协同治疗肝细胞癌

Low-density lipoprotein decorated silica nanoparticles co-delivering sorafenib and doxorubicin for effective treatment of hepatocellular carcinoma.

机构信息

a Department of Hepato-Biliary-Pancreatic Surgery , First Hospital of Jilin University , Changchun , PR China.

出版信息

Drug Deliv. 2018 Nov;25(1):2007-2014. doi: 10.1080/10717544.2018.1531953.

Abstract

Combinational therapy is usually considered as a preferable approach for effective cancer therapy. Especially, combinational chemotherapies targeting different molecular targets are of particular interest due to its high flexibility as well as efficiency. In our study, the surface of silica nanoparticles (SLN) was modified with low-density lipoprotein (LDL) to construct platform (LDL-SLN) capable of specifically targeting low-density lipoprotein receptors (LDLRs) that overexpressing in hepatocellular carcinoma (HCC). In addition, the versatile drug loading capacity of LDL-SLN was employed to fabricate a preferable drug delivery system to co-deliver sorafenib (Sor) and doxorubicin (Dox) for combinational chemotherapy of HCC. Our results revealed that the LDL-SLN/Sor/Dox nanoparticles with size around 100 nm showed preferable stability in physiological environments. Moreover, the LDL-SLN/Sor/Dox could target LDLR overexpressed HepG2 cells. More importantly, both in vitro and in vivo experiments demonstrated that the LDL-SLN/Sor/Dox exerted elevated antitumor efficacy compared to Sor or Dox alone, which indicated that LDL-SLN/Sor/Dox could be a powerful tool for effective combinational chemotherapy of HCC.

摘要

联合治疗通常被认为是一种有效的癌症治疗方法。特别是,针对不同分子靶点的联合化疗因其高灵活性和高效性而备受关注。在我们的研究中,将硅纳米粒子(SLN)的表面用低密度脂蛋白(LDL)修饰,构建了能够特异性靶向在肝癌(HCC)中过度表达的低密度脂蛋白受体(LDLR)的平台(LDL-SLN)。此外,LDL-SLN 的多功能药物负载能力被用于构建一种更优的药物输送系统,以共递索拉非尼(Sor)和阿霉素(Dox),用于 HCC 的联合化疗。我们的结果表明,尺寸约为 100nm 的 LDL-SLN/Sor/Dox 纳米粒在生理环境中表现出更好的稳定性。此外,LDL-SLN/Sor/Dox 可以靶向 LDLR 过度表达的 HepG2 细胞。更重要的是,体外和体内实验均表明,与单独使用 Sor 或 Dox 相比,LDL-SLN/Sor/Dox 发挥了更高的抗肿瘤疗效,这表明 LDL-SLN/Sor/Dox 可能是 HCC 有效联合化疗的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb0/6319454/956a84835803/IDRD_A_1531953_F0001_B.jpg

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