Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy

Yelee Kim, Jiwoong Choi, Eun Hye Kim, Wonbeom Park, Hochung Jang, Yeongji Jang, Sung Gil Chi, Dae Hyuk Kweon, Kyuri Lee, Sun Hwa Kim, Yoosoo Yang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
JournalAdvanced Science
DOIs
Publication statusAccepted/In press - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords

  • cancer immunotherapy
  • lipid nanoparticle
  • mRNA delivery
  • tumor-targeted delivery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Chemical Engineering
  • General Materials Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Engineering
  • General Physics and Astronomy

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