김선화 (한국과학기술연구원(KIST), 고려대학교) | 한빛사논문 > 한빛사

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한국과학기술연구원(KIST), 고려대학교

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Adv. Sci., Mar 23 2024, | https://doi.org/10.1002/advs.202309917 Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy

Yelee Kim ^{1 2}, Jiwoong Choi ¹, Eun Hye Kim ^{1 2}, Wonbeom Park ³, Hochung Jang ^{1 4}, Yeongji Jang ^{1 2}, Sung-Gil Chi ², Dae-Hyuk Kweon ³, Kyuri Lee ⁵, Sun Hwa Kim ^{1 6 *}, Yoosoo Yang ^{1 4 *}

¹Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
²Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
³Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
⁴Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
⁵College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
⁶KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.

^*Corresponding authors: correspondence to Sun Hwa Kim or Yoosoo Yang

Abstract

Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue-specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor-targeting peptides into the LNPs; the programmed death ligand 1 (PD-L1) binding peptides are conjugated to PEGylated lipids via a copper-free click reaction, and directly incorporated into the LNP composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD-L1 proteins, which leads to the uptake of LNPs into PD-L1 overexpressing cancer cells both in vitro and in vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, mRNA encoding phosphatase and tensin homolog (PTEN) is delivered via Pep LNPs to PTEN-deficient triple-negative breast cancers (TNBCs). Pep LNPs loaded with PTEN mRNA specifically promotes autophagy-mediated immunogenic cell death in 4T1 tumors, resulting in effective anticancer immune responses. This study highlights the potential of tumor-targeted LNPs for mRNA-based cancer therapy.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-25)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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