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用β1整合素结合适体靶向三阴性乳腺癌细胞。

Targeting triple-negative breast cancer cells with a β1-integrin binding aptamer.

作者信息

Pleiko Karlis, Haugas Maarja, Parfejevs Vadims, Pantelejevs Teodors, Parisini Emilio, Teesalu Tambet, Riekstina Una

机构信息

Faculty of Medicine, University of Latvia, House of Science, Jelgavas Str. 3, 1004 Riga, Latvia.

Laboratory of Precision- and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.

出版信息

Mol Ther Nucleic Acids. 2023 Aug 16;33:871-884. doi: 10.1016/j.omtn.2023.08.015. eCollection 2023 Sep 12.

Abstract

Targeted therapies have increased the treatment options for triple-negative breast cancer patients. However, the paucity of targetable biomarkers and tumor heterogeneity have limited the ability of precision-guided interventions to live up to their full potential. As affinity-targeting ligands, aptamers show high selectivity toward target molecules. Compared with antibodies, aptamers have lower molecular weight, increased stability during transportation, reduced immunogenicity, and increased tissue uptake. Recently, we reported discovery of the GreenB1 aptamer, which is internalized in cultured triple-negative MDA-MB-231 human breast cancer cells. We show that the GreenB1 aptamer specifically targets β1-integrin, a protein linked previously to breast cancer cell invasiveness and migration. Aptamer binds to β1-integrin with low nanomolar affinity. Our findings suggest potential applications for GreenB1-guided precision agents for diagnosis and therapy of cancers overexpressing β1-integrin.

摘要

靶向治疗增加了三阴性乳腺癌患者的治疗选择。然而,可靶向生物标志物的匮乏和肿瘤异质性限制了精准导向干预充分发挥其潜力的能力。作为亲和靶向配体,适体对靶分子表现出高选择性。与抗体相比,适体分子量更低,运输过程中稳定性增强,免疫原性降低,组织摄取增加。最近,我们报告发现了GreenB1适体,它可被培养的三阴性MDA-MB-231人乳腺癌细胞内化。我们表明,GreenB1适体特异性靶向β1整合素,该蛋白先前与乳腺癌细胞的侵袭和迁移有关。适体以低纳摩尔亲和力与β1整合素结合。我们的研究结果表明,GreenB1导向的精准药物在诊断和治疗过表达β1整合素的癌症方面具有潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e8/10481362/ac978b98ca92/fx1.jpg

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