Kim, Eun Hye Lee, Jongwon Kwak, Gijung Jang, Hochung Kim, Hyosuk Cho, Haeun Jang, Yeongji Choi, Jiwoong Chi, Sung Gil Kim, Kwangmeyung Kwon, Ick Chan Yang, Yoosoo Kim, Sun Hwa 2024-01-19T12:02:55Z 2024-01-19T12:02:55Z 2022-05-12 2022-05 0168-3659 https://pubs.kist.re.kr/handle/201004/115232 Upregulation of oncogenic miRNA21 (miR-21) plays a pivotal role in proliferation, migration and invasion of cancer cells. In addition to cancer cells, tumor-associated macrophages (TAMs) also have high abundance of miR21, which accelerates malignant progression of tumors in the late stages of carcinogenesis. Despite of the protumorigenic functions of miR-21 in TAMs and cancer cells, reliable therapeutic strategies to simultaneously inhibit miR-21 activity in both types of cell have not yet been developed. In this study, we designed a dualtargeting 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. Our studies found that Pep-21 treatment reduced tumor cell migration, reprogrammed immunosuppressive M2-type TAMs into M1-type macrophages, and restrained tumor progression. Collectively, neutralization of miR-21 activity in both cancer cells and TAMs can be a promising strategy for effective antitumor responses. English Elsevier BV PDL1-binding peptide/anti-miRNA21 conjugate as a therapeutic modality for PD-L1high tumors and TAMs Article 10.1016/j.jconrel.2022.02.031 1 Journal of Controlled Release, v.345, pp.62 - 74 Journal of Controlled Release 345 62 74 N scie scopus 000783878100001 2-s2.0-85125879435 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Editorial Material IN-VIVO CANCER MICRORNAS OLIGONUCLEOTIDES anti-miRNA delivery PD-L1 miR-21 B16 melanoma Tumor-associated macrophage