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首页> 美国卫生研究院文献>Pharmaceutics >The Importance of Poly(ethylene glycol) and Lipid Structure in Targeted Gene Delivery to Lymph Nodes by Lipid Nanoparticles
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The Importance of Poly(ethylene glycol) and Lipid Structure in Targeted Gene Delivery to Lymph Nodes by Lipid Nanoparticles

机译：聚（乙二醇）和脂质结构在脂质纳米颗粒靶向基因递送至淋巴结中的重要性

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Targeted delivery of nucleic acids to lymph nodes is critical for the development of effective vaccines and immunotherapies. However, it remains challenging to achieve selective lymph node delivery. Current gene delivery systems target mainly to the liver and typically exhibit off-target transfection at various tissues. Here we report novel lipid nanoparticles (LNPs) that can deliver plasmid DNA (pDNA) to a draining lymph node, thereby significantly enhancing transfection at this target organ, and substantially reducing gene expression at the intramuscular injection site (muscle). In particular, we discovered that LNPs stabilized by 3% Tween 20, a surfactant with a branched poly(ethylene glycol) (PEG) chain linking to a short lipid tail, achieved highly specific transfection at the lymph node. This was in contrast to conventional LNPs stabilized with a linear PEG chain and two saturated lipid tails (PEG-DSPE) that predominately transfected at the injection site (muscle). Interestingly, replacing Tween 20 with Tween 80, which has a longer unsaturated lipid tail, led to a much lower transfection efficiency. Our work demonstrates the importance of PEGylation in selective organ targeting of nanoparticles, provides new insights into the structure–property relationship of LNPs, and offers a novel, simple, and practical PEGylation technology to prepare the next generation of safe and effective vaccines against viruses or tumours.
机译：针对核酸向淋巴结的靶向递送对于有效疫苗和免疫治疗的发展至关重要。然而，实现选择性淋巴结交付仍然挑战。目前的基因递送系统主要针对肝脏，并且通常在各种组织中表现出靶靶转染。在这里，我们报告了可以将质粒DNA（PDNA）递送到排水淋巴结的新型脂质纳米颗粒（LNP），从而显着增强该靶器官的转染，并大大降低肌内注射部位（肌肉）的基因表达。特别地，我们发现LNP稳定3％吐温20，用支化聚（乙二醇）（PEG）链接到短脂尾的表面活性剂，在淋巴结在淋巴结达到高度的转染。这与用线性PEG链和两个饱和脂尾（PEG-DSPE）稳定的常规LNP形成对比，其主要在注射部位（肌肉）上。有趣的是，用吐温80代替具有较长的不饱和脂尾的吐温20，导致了更低的转染效率。我们的工作证明了聚乙二醇化在纳米粒子的选择性器官靶向中的重要性，为LNP的结构性质关系提供了新的见解，并提供了一种新颖，简单，实用的PEG化技术，用于制备针对病毒的下一代安全和有效疫苗或肿瘤。

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