ArticleInternational journal of nanomedicine2025
Lipid Nanoparticles Formulated with a Novel Cholesterol-Tailed Ionizable Lipid Markedly Increase mRNA Delivery Both in vitro and in vivo.
Article in International journal of nanomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Rewriting the mRNA Delivery Map: Albumin Hitchhiking Lipid Nanoparticles for Safer and Smarter Nanomedicine.ACS materials Au · 2026Review
- Article
- Nanodelivery of Traditional Chinese Medicine Monomers: An Emerging Strategy to Reprogram the Immunosuppressive Tumor Microenvironment.International journal of nanomedicine · 2026Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Lipid nanoparticles (LNPs) have emerged as the most successful, effective, and safe method for RNA delivery, and have shown tremendous potential for the treatment of various diseases, such as messenger RNA (mRNA) vaccines, gene editing, and RNA interface (RNAi) therapies. The development of novel ionizable lipids holds great promise in improving the efficacy and safety of LNPs. Methods: We synthesized a novel ionizable lipid, ARV-T1, with a cholesterol moiety incorporated in its tail. We characterized the physicochemical properties of LNPs formulated with ARV-T1, calculated the pKa of ARV-T1, and conducted in vitro and in vivo mRNA delivery studies. Results: ARV-T1 has a pKa value of 6.73, and compared to SM-102, the ionizable lipid used in the Moderna SARS-CoV2 vaccine, the LNPs formulated with ARV-T1 showed smaller particle sizes, lower polydispersity indices, and higher absolute zeta potential values. More importantly, the LNPs formulated with ARV-T1 showed significantly increased mRNA delivery both in vitro and in vivo, markedly increased protein expression, and demonstrated more than 10-fold higher potency in inducing SARS-CoV-2 spike protein binding antibodies and SARS-CoV-2 virus neutralizing antibodies in mice compared to the LNPs formulated with SM-102. Furthermore, the unique ester linkage of ARV-T1 enables rapid and complete metabolism in vivo, thereby improving its biocompatibility and safety profile. Conclusion: These findings suggest that the novel ionizable lipid ARV-T1 holds great promise for the development of mRNA vaccines and other mRNA-based therapeutics and may pave the way for the development of safer and more effective mRNA delivery systems.
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