Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12–200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration.

中文翻译：

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用于将 RNA 输送到中枢神经系统的可电离纳米乳液——扩散性的重要性


脂质纳米颗粒 (LNP) 目前在 RNA 递送领域占据主导地位；然而，它们有限的扩散性阻碍了靶向组织的扩散，因此阻碍了它们细胞内药物递送的能力。这对于中枢神经系统（CNS）等组织尤其重要，在这些组织中，克服主动脑屏障对于基因治疗的功效至关重要。这项研究旨在创建可电离纳米乳液 (iNE)，这是一种具有增强扩散性的新一代 RNA 递送系统。所开发的 iNE（由 C12–200、DOPE、维生素 E 和 DMG-PEG 组合而成）尺寸小于 100 nm、中性表面电荷和高 RNA 负载能力，在各种细胞中表现出优异的细胞活力和转染效率模型，包括神经元、星形胶质细胞和小胶质细胞。随后，对含有 mRNA GFP 的 iNE 进行了中枢神经系统转染测试，强调了它们在实质内给药后卓越的扩散性和神经元的选择性转染。