Lipid nanoparticles deliver mRNA to the blood–brain barrier

IF 9.5 2区材料科学 Q1 CHEMISTRY, PHYSICAL

Nano Research Pub Date : 2024-08-01 DOI:10.1007/s12274-024-6827-7

Yanina Kuzminich, Avraham Shakked, Randi Calkins, Sebastian Rudden, Camille Jones, Jessie Doan, Bora Jang, Elisa Schrader Echeverri, Ryan Zenhausern, Liming Lian, David Loughrey, Hannah E. Peck, Rachelle Wiese, Dorothy Koveal, Philip J. Santangelo, James E. Dahlman

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Abstract

Lipid nanoparticles (LNPs) have delivered RNA to hepatocytes in patients after intravenous administration. These clinical data support efforts to design LNPs that transfect cells in the central nervous system (CNS). However, delivery to the CNS has been difficult, in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains challenging. Here we report methods to isolate different cell types from the CNS, and subsequently present mRNA delivery readouts using a liver-detargeted LNP. These data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous administration. Given the difficulty of crossing the blood–brain barrier, they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

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将 mRNA 运送到血脑屏障的脂质纳米颗粒

脂质纳米粒子（LNPs）可在静脉注射后将 RNA 运送到患者的肝细胞中。这些临床数据为设计可转染中枢神经系统（CNS）细胞的 LNPs 提供了支持。然而，向中枢神经系统递送RNA一直是个难题，这在很大程度上是因为在成年小鼠中量化靶上递送和常见的非靶细胞类型仍然是个挑战。在此，我们报告了从中枢神经系统中分离不同细胞类型的方法，并随后介绍了使用肝脏靶向 LNP 的 mRNA 递送读数。这些数据表明，不含靶向配体的 LNPs 可以在静脉注射后转染小鼠的脑内皮细胞。由于难以穿越血脑屏障，这些数据还强调了以细胞类型分辨率而非全组织分辨率量化中枢神经系统内递送的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Research 化学-材料科学：综合

CiteScore

14.30

自引率

11.10%

发文量

2574

审稿时长

1.7 months

期刊介绍： Nano Research is a peer-reviewed, international and interdisciplinary research journal that focuses on all aspects of nanoscience and nanotechnology. It solicits submissions in various topical areas, from basic aspects of nanoscale materials to practical applications. The journal publishes articles on synthesis, characterization, and manipulation of nanomaterials; nanoscale physics, electrical transport, and quantum physics; scanning probe microscopy and spectroscopy; nanofluidics; nanosensors; nanoelectronics and molecular electronics; nano-optics, nano-optoelectronics, and nano-photonics; nanomagnetics; nanobiotechnology and nanomedicine; and nanoscale modeling and simulations. Nano Research offers readers a combination of authoritative and comprehensive Reviews, original cutting-edge research in Communication and Full Paper formats. The journal also prioritizes rapid review to ensure prompt publication.