دورية أكاديمية
Polyphenolic Nanoparticle Platforms (PARCELs) for In Vitro and In Vivo mRNA Delivery.
العنوان: | Polyphenolic Nanoparticle Platforms (PARCELs) for In Vitro and In Vivo mRNA Delivery. |
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المؤلفون: | Ma Y; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States., Tiwade PB; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States., VanKeulen-Miller R; Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States., Narasipura EA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States., Fenton OS; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States. |
المصدر: | Nano letters [Nano Lett] 2024 May 22; Vol. 24 (20), pp. 6092-6101. Date of Electronic Publication: 2024 May 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101088070 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6992 (Electronic) Linking ISSN: 15306984 NLM ISO Abbreviation: Nano Lett Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c2001- |
مواضيع طبية MeSH: | Polyphenols*/chemistry , RNA, Messenger*/genetics , Nanoparticles*/chemistry, Animals ; Mice ; Humans ; SARS-CoV-2/drug effects ; COVID-19 ; Drug Delivery Systems ; Tissue Distribution ; Lipids/chemistry ; Endosomes/metabolism ; Liposomes |
مستخلص: | 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 p olyphenolic n a nopa r ti c l e p l atforms (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 in vitro mechanism and activity, ultimately highlighting the superior endosomal escape properties of PARCELs relative to analogous LNPs. Finally, we examine the in vivo 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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معلومات مُعتمدة: | P50 HD103573 United States HD NICHD NIH HHS; P30 NS045892 United States NS NINDS NIH HHS; K12 TR004416 United States TR NCATS NIH HHS; R21 EB034942 United States EB NIBIB NIH HHS; P30 CA016086 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: delivery platforms; endosomal escape; lipid nanoparticles; mRNA; polyphenol |
المشرفين على المادة: | 0 (Lipid Nanoparticles) |
تواريخ الأحداث: | Date Created: 20240510 Date Completed: 20240522 Latest Revision: 20240704 |
رمز التحديث: | 20240704 |
مُعرف محوري في PubMed: | PMC11218425 |
DOI: | 10.1021/acs.nanolett.4c01235 |
PMID: | 38728297 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1530-6992 |
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DOI: | 10.1021/acs.nanolett.4c01235 |