DataVXACS NanoPaper
journal article·2024-08-27

Low-Dose Mildronate-Derived Lipidoids for Efficient mRNA Vaccine Delivery with Minimal Inflammation Side Effects

Jiwei Liu, Bing Xiao, Yongle Yang, Yifan Jiang, Rui Wang, Qi Wei, Yixuan Pan, Yuping Chen, Huimin Wang, Jiaqi Fan, Ruoshui Li, Haoran Xu, Ying Piao, Jiajia Xiang, Shiqun Shao, Zhuxian Zhou, Youqing Shen, Wenjing Sun, Jianbin Tang

ACS Nano· Volume 18· Issue 34
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Source abstract

Abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · Lipid Membrane Structure and Behavior

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China

Institute of Pharmaceutics, Zhejiang Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China

ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, P. R. China

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P. R. China

Funding

National Key Research and Development Program of China · Science and Technology Department of Zhejiang Province · National Natural Science Foundation of China · 2023 Hangzhou West Lake Pearl Project Leading Innovative Youth Team Project

References (43)

Show source-provided references
1. 10.1016/j.addr.2020.12.01410.1016/j.addr.2020.12.014 ↗
2. 10.3390/pharmaceutics1202010210.3390/pharmaceutics12020102 ↗
3. 10.1021/acsnano.1c0184510.1021/acsnano.1c01845 ↗
4. 10.1038/mt.2012.20210.1038/mt.2012.202 ↗
5. 10.1093/nar/29.18.388210.1093/nar/29.18.3882 ↗
6. 10.1038/nrd427810.1038/nrd4278 ↗
7. 10.3389/fimmu.2022.88712510.3389/fimmu.2022.887125 ↗
8. 10.1016/j.addr.2023.11499310.1016/j.addr.2023.114993 ↗
9. 10.1186/s12943-021-01311-z10.1186/s12943-021-01311-z ↗
10. 10.1016/j.ymthe.2019.01.02010.1016/j.ymthe.2019.01.020 ↗
11. 10.1016/j.addr.2020.06.02210.1016/j.addr.2020.06.022 ↗
12. 10.1016/j.nantod.2018.10.00510.1016/j.nantod.2018.10.005 ↗
13. 10.1016/j.smim.2013.05.00110.1016/j.smim.2013.05.001 ↗
14. 10.26355/eurrev_202102_2487710.26355/eurrev_202102_24877 ↗
15. 10.1056/NEJMc203624210.1056/NEJMc2036242 ↗
16. 10.1056/NEJMoa202790610.1056/NEJMoa2027906 ↗
17. 10.1038/natrevmats.2017.5610.1038/natrevmats.2017.56 ↗
18. 10.1016/j.ymthe.2019.02.01210.1016/j.ymthe.2019.02.012 ↗
19. 10.1021/cr800409e10.1021/cr800409e ↗
20. 10.1016/j.chemphyslip.2020.10503210.1016/j.chemphyslip.2020.105032 ↗
21. 10.1002/adtp.20200009910.1002/adtp.202000099 ↗
22. 10.1021/bc300381s10.1021/bc300381s ↗
23. 10.1021/bc900393r10.1021/bc900393r ↗
24. 10.1002/anie.20180905610.1002/anie.201809056 ↗
25. 10.1529/biophysj.106.08376610.1529/biophysj.106.083766 ↗
26. 10.3748/wjg.v12.i40.642910.3748/wjg.v12.i40.6429 ↗
27. 10.1073/pnas.080825610510.1073/pnas.0808256105 ↗
28. 10.1038/s41467-020-14527-210.1038/s41467-020-14527-2 ↗
29. 10.1016/j.bbamem.2012.03.00910.1016/j.bbamem.2012.03.009 ↗
30. 10.1038/nrm233010.1038/nrm2330 ↗
31. 10.1038/s41563-020-00886-010.1038/s41563-020-00886-0 ↗
32. 10.1371/journal.pone.024100610.1371/journal.pone.0241006 ↗
33. 10.3390/jcm1007142810.3390/jcm10071428 ↗
34. 10.1007/s10900-021-01039-310.1007/s10900-021-01039-3 ↗
35. 10.1038/s41590-022-01160-y10.1038/s41590-022-01160-y ↗
36. 10.1002/adma.20220747110.1002/adma.202207471 ↗
37. 10.3390/medicina4710007810.3390/medicina47100078 ↗
38. 10.1039/C6CC08241F10.1039/C6CC08241F ↗
39. 10.1016/j.aca.2017.01.06210.1016/j.aca.2017.01.062 ↗
40. 10.1016/j.jconrel.2021.03.04310.1016/j.jconrel.2021.03.043 ↗
41. 10.1021/jacs.1c0958510.1021/jacs.1c09585 ↗
42. 10.1002/adma.20180530810.1002/adma.201805308 ↗
43. 10.2353/ajpath.2008.07050210.2353/ajpath.2008.070502 ↗