Anti-MUC1/CD44 Dual-Aptamer-Conjugated Liposomes for Cotargeting Breast Cancer Cells and Cancer Stem Cells

抗 MUC1/CD44 双适体结合脂质体用于共靶向乳腺癌细胞和癌症干细胞

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作者:Dong-Min Kim, Minhee Kim, Hee-Bin Park, Keun-Sik Kim, Dong-Eun Kim

Abstract

In this study, we developed a drug-loading liposome linked with two types of DNA aptamers targeting the surface marker transmembrane glycoprotein mucin 1 antigen (MUC1) on breast cancer cells and cell surface glycoprotein CD44 antigen (CD44) on their cancer stem cells (CSCs). Dual-aptamer-conjugated liposomes, called dual-aptamosomes, were prepared to encapsulate doxorubicin (Dox) and tested for Dox delivery to the 3D-cultured breast cancer cells as well as CSCs. Dox was readily delivered into the cancer cells via ligand-mediated cellular uptake of dual-aptamosomes. Dual-aptamosomes harboring Dox (dual-Apt-Dox) showed a significantly higher cytotoxicity to both CSCs and cancer cells than to liposomes lacking the aptamers. Furthermore, we demonstrated inhibitory activity of dual-Apt-Dox against metastasis of breast cancer stems cells in athymic nude mice. Thus, the dual-aptamer-conjugated liposomal system can be a useful drug delivery carrier for treatment of breast cancer, given its efficiency in targeting both breast cancer cells and their CSCs.

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