Low-Dose Mildronate-Derived Lipidoids for Efficient mRNA Vaccine Delivery with Minimal Inflammation Side Effects
mRNA vaccines have been revolutionizing disease prevention and treatment. However, their further application is hindered by inflammatory side effects, primarily caused by delivery systems such as lipid nanoparticles (LNPs). In response to this issue, we prepared cationic lipids (mLPs) derived from mildronate, a small-molecule drug, and subsequently developed the LNP (mLNP-69) comprising a low dose of mLP. Compared with the LNP (sLNP) based on SM-102, a commercially available ionizable lipid, mLNP-69 ensures effective mRNA delivery while significantly reducing local inflammation. In preclinical prophylactic and therapeutic B16-OVA melanoma models, mLNP-69 demonstrated successful mRNA cancer vaccine delivery in vivo, effectively preventing tumor occurrence or impeding tumor progression. The results suggest that the cationic lipids derived from mildronate, which exhibit efficient delivery capabilities and minimal inflammatory side effects, hold great promise for clinical application.
Authors
- Shiqun Shao (ORCID: https://orcid.org/0000-0001-7029-3791)
- Youqing Shen (ORCID: https://orcid.org/0000-0003-1837-7976)
- Jianbin Tang (ORCID: https://orcid.org/0000-0003-4498-5705)
- Yong‐Le Yang (ORCID: https://orcid.org/0000-0002-3266-8019)
- Jiajia Xiang (ORCID: https://orcid.org/0000-0001-5404-0735)
- Zhuxian Zhou (ORCID: https://orcid.org/0000-0002-7104-9915)
- Bing Xiao (ORCID: https://orcid.org/0000-0002-3350-2678)
- Yixuan Pan
- Ying Piao
- Jiwei Liu (ORCID: https://orcid.org/0000-0002-4010-3026)
- Wenjing Sun (ORCID: https://orcid.org/0009-0001-2267-9195)
- Jiaqi Fan (ORCID: https://orcid.org/0000-0002-1909-9026)
- Rui Wang (ORCID: https://orcid.org/0009-0009-7636-1586)
- Yuping Chen (ORCID: https://orcid.org/0000-0001-8562-0804)
- Wei Dong Qi (ORCID: https://orcid.org/0000-0002-7378-1392)
- Haoran Xu (ORCID: https://orcid.org/0000-0002-9943-6423)
- Ruoshui Li (ORCID: https://orcid.org/0000-0003-3922-686X)
- Yifan Jiang (ORCID: https://orcid.org/0000-0002-9737-2542)
- Huimin Wang (ORCID: https://orcid.org/0009-0000-4062-561X)
Institutions
- Zhejiang University of Science and Technology (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- ACS Nano
- Published
- 2024-08-16
- DOI
- https://doi.org/10.1021/acsnano.4c06160
- Citations
- 16
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 3.74
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Science and Technology Department of Zhejiang Province