Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment
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DOI：
10.1016/j.ijpharm.2012.05.018
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发表时间：
2012-09-15
影响因子：
5.8
通讯作者：
Moreira, Joao N.
中科院分区：
文献类型：
--
作者：
Gomes-da-Silva, Ligia C.;Santos, Adriana O.;Moreira, Joao N.
目前的工作旨在设计一种基于脂质的纳米载体，用于将 siRNA 递送至乳腺肿瘤内的两个细胞亚群，即癌症和来自血管生成肿瘤血管的内皮细胞。为了实现这一目标，使用在这两个亚群上过表达的核仁素特异性内化的 F3 肽作为靶向部分。开发的 F3 靶向稳定核酸脂质颗粒为全身给药提供了足够的特征。此外，F3肽附着在脂质体表面上使得癌细胞和血管生成血管的内皮细胞能够内化，其内化程度显着高于在非癌细胞中观察到的内化程度。与非靶向脂质体相比，在通过 F3 靶向脂质体递送抗 eGFP siRNA 后，进一步观察到 eGFP 过表达的人类癌细胞系中增强型绿色荧光蛋白 (eGFP) 在蛋白质和 mRNA 水平上的序列特异性下调。这种效应高度依赖于聚乙二醇 (PEG) 的含量，siRNA 和溶酶体之间的共定位研究证明了这一点。总体而言，目前的工作在细胞和分子水平上对乳腺癌中具有多靶向能力的纳米颗粒做出了重要贡献。 (c) 2012 Elsevier B.V. 保留所有权利。
The present work aimed at designing a lipid-based nanocarrier for siRNA delivery toward two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety.The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non-cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co-localization studies between the siRNA and the lysosomes.Overall, the present work represents an important contribution toward a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level. (c) 2012 Elsevier B.V. All rights reserved.