Jun Hyeong Hong, Jae Hoon Kim, Seung-Yeul Lee, Ha Yeon Park, Sin A Park, Han Sang Kim, Bumhee Lim, Jae-Eon Lee, So Yeon Jeong, Yong Hyun Jeon, Tae Jeong Oh, Jaewook Lee, Sungwhan An
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引用次数: 0
Abstract
Intravenously administered lipid nanoparticles (LNPs) predominantly accumulate in the liver, limiting mRNA delivery to extrahepatic tissues, particularly the central nervous system (CNS). Here, we report a ligand-free strategy for systemic CNS delivery using phosphatidylserine (PS, 1 mol %)-engineered LNPs, in which cholesterol is replaced with protopanaxadiol (PPD) or ginsenoside Rg2. Following intravenous administration of luciferase mRNA, in vivo and ex vivo bioluminescence imaging demonstrated robust protein expression in both the brain and spinal cord with PS-containing LNPs, whereas PS-free formulations showed minimal CNS-associated expression. Increasing PS content from 1 to 4 mol % reduced brain expression while enhancing splenic accumulation, revealing PS-dependent regulation of LNP biodistribution. These findings establish low-level PS incorporation as a tunable strategy for systemic mRNA delivery to the CNS and provide a potential platform for CNS-targeted nucleic acid therapeutics.
期刊介绍：
ACS Materials Letters is a journal that publishes high-quality and urgent papers at the forefront of fundamental and applied research in the field of materials science. It aims to bridge the gap between materials and other disciplines such as chemistry, engineering, and biology. The journal encourages multidisciplinary and innovative research that addresses global challenges. Papers submitted to ACS Materials Letters should clearly demonstrate the need for rapid disclosure of key results. The journal is interested in various areas including the design, synthesis, characterization, and evaluation of emerging materials, understanding the relationships between structure, property, and performance, as well as developing materials for applications in energy, environment, biomedical, electronics, and catalysis. The journal has a 2-year impact factor of 11.4 and is dedicated to publishing transformative materials research with fast processing times. The editors and staff of ACS Materials Letters actively participate in major scientific conferences and engage closely with readers and authors. The journal also maintains an active presence on social media to provide authors with greater visibility.
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