AI Article Synopsis
- Lipid nanoparticles (LNPs) have issues with mRNA delivery due to endosomal trapping, which limits their effectiveness despite their use in COVID-19 vaccines.
- Researchers introduce olyphenolic nanopatil platforms (PARCELs) as new tools for mRNA delivery, starting with a thorough structural analysis of various polyphenols.
- The study shows that PARCELs have better endosomal escape, enhanced biodistribution, and improved therapeutic effects in mice compared to LNPs, aiming to establish them as a safer and more efficient delivery method for mRNA-based therapies.
Article Abstract
Despite their successful implementation in the COVID-19 vaccines, lipid nanoparticles (LNPs) still face a central limitation in the delivery of mRNA payloads: endosomal trapping. Improving upon this inefficiency could afford improved drug delivery systems, paving the way toward safer and more effective mRNA-based medicines. Here, we present olyphenolic nnopatil patforms (PARCELs) as effective mRNA delivery systems. In brief, our investigation begins with a computationally guided structural analysis of 1825 discrete polyphenolic structural data points across 73 diverse small molecule polyphenols and 25 molecular parameters. We then generate structurally diverse PARCELs, evaluating their mechanism and activity, ultimately highlighting the superior endosomal escape properties of PARCELs relative to analogous LNPs. Finally, we examine the biodistribution, protein expression, and therapeutic efficacy of PARCELs in mice. In undertaking this approach, the goal of this study is to establish PARCELs as viable delivery platforms for safe and effective mRNA delivery.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218425 | PMC |
| http://dx.doi.org/10.1021/acs.nanolett.4c01235 | DOI Listing |
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