Kim, Yelee Choi, Jiwoong Kim, Eun Hye Park, Wonbeom Jang, Hochung Jang, Yeongji Chi, Sung-Gil Kweon, Dae-Hyuk Lee, Kyuri Kim, Sun Hwa Yang, Yoosoo 2024-04-11T02:00:26Z 2024-04-11T02:00:26Z 2024-04-11 2024-06 https://pubs.kist.re.kr/handle/201004/149617 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. This study investigates a targeted delivery method for cancer therapy, using programmed death ligand 1 (PD-L1)-targeting lipid nanoparticles (LNPs) with PD-L1 binding peptides attached via a copper-free click reaction. This approach turns on phosphatase and tensin homolog (PTEN) in triple-negative breast cancers (TNBCs), boosting autophagy, inducing immunogenic cell death (ICD)-associated damage-associated molecular patterns (DAMPs), promoting dendritic cell (DC) maturation, and facilitating T-cell migration to tumors. This findings highlight the promising potential of mRNA-based cancer therapy using these targeted LNPs. image English Wiley-VCH Verlag Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy Article 10.1002/advs.202309917 1 Advanced Science, v.11, no.22 Advanced Science 11 22 Y scie scopus 001189384900001 2-s2.0-85188356881 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article MESSENGER-RNA DELIVERY MEDIATED DELIVERY IMMUNE-RESPONSES PD-L1 EXPRESSION GENE-THERAPY TUMOR-GROWTH AUTOPHAGY PROSTATE SURVIVAL VECTORS cancer immunotherapy lipid nanoparticle mRNA delivery tumor-targeted delivery