| 초록 |
Upregulation of oncogenic miRNA-21 (miR-21) plays a pivotal role in cancer development. In addition to cancer cells, tumor-associated macrophages (TAMs) also have high abundance of miR-21, which accelerates malignant progression of tumors in the late stages of carcinogenesis. In this study, we designed a dual-targeting drug delivery system of miR-21 inhibitors that could bind to both tumor cells and macrophages with overexpressed PD-L1 receptors. This peptide-oligonucleotide conjugate (Pep-21) consists of a PDL1-binding peptide covalently linked with an anti-miR-21 inhibitor via click chemistry. Pep-21 was preferentially internalized in both cell types, consequently depleting endogenous miR-21. We also found that Pep-21 reduced tumor cell migration, reprogrammed TAMs into M1-type macrophages, and restrained tumor progression. Collectively, neutralizationof miR-21 activity in both cancer cells and TAMs can be a promising strategy for effective antitumor responses. |
