PDL1-binding peptide/anti-miRNA21 conjugate as a therapeutic modality for PD-L1high tumors and TAMs

Eun Hye Kim, Jongwon Lee, Gijung Kwak, Hochung Jang, Hyosuk Kim, Haeun Cho, Yeongji Jang, Jiwoong Choi, Sung Gil Chi, Kwangmeyung Kim, Ick Chan Kwon, Yoosoo Yang, Sun Hwa Kim

Research output: Contribution to journalEditorial

Abstract

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 miR-21, which accelerates malignant progression of tumors in the late stages of carcinogenesis. Despite of the pro-tumorigenic 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 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. 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.

Original languageEnglish
Pages (from-to)62-74
Number of pages13
JournalJournal of Controlled Release
Volume345
DOIs
StatePublished - May 2022

Keywords

  • anti-miRNA delivery
  • B16 melanoma
  • miR-21
  • PD-L1
  • Tumor-associated macrophage

Fingerprint

Dive into the research topics of 'PDL1-binding peptide/anti-miRNA21 conjugate as a therapeutic modality for PD-L1high tumors and TAMs'. Together they form a unique fingerprint.

Cite this