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

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

doi:10.1016/j.omtn.2023.08.015

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

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

Authors

Karlis Pleiko^{1

2}, Maarja Haugas², Vadims Parfejevs¹, Teodors Pantelejevs³, Emilio Parisini^{3

4}, Tambet Teesalu^{2

5}, Una Riekstina¹

Affiliations

¹ Faculty of Medicine, University of Latvia, House of Science, Jelgavas Str. 3, 1004 Riga, Latvia.
² Laboratory of Precision- and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
³ Latvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, Latvia.
⁴ Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
⁵ Materials Research Laboratory, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.

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.

Keywords: MT: Oligonucleotides: Therapies and Applications; affinity ligands; aptamer; aptamer internalization; proximity labeling; triple-negative breast cancer; β1-integrin.