Phosphatidylserine Lipid Nanoparticles Promote Systemic RNA Delivery to Secondary Lymphoid Organs
Phosphatidylserine Lipid Nanoparticles Promote Systemic RNA Delivery to Secondary Lymphoid Organs
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DOI：
10.1021/acs.nanolett.2c03234
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发表时间：
2022-10-04
期刊：
影响因子：
10.8
通讯作者：
Jiang, Shaoyi
中科院分区：
文献类型：
--
作者：
Luozhong, Sijin;Yuan, Zhefan;Jiang, Shaoyi
次级淋巴器官（SLO）是各种应用中mRNA递送的重要靶标。虽然目前的递送方法依赖于通过肌内（IM）或皮下（SC）注射将纳米颗粒引流到淋巴结，但是非常需要通过全身施用（IV）用于SLO靶向递送的有效mRNA递送载体，但尚未获得。在这项研究中，我们开发了一种有效的SLO靶向载体使用磷脂酰丝氨酸（PS），一个众所周知的信号分子，促进吞噬细胞的内吞活性和包膜病毒的细胞进入。我们采用了这些仿生策略，并将PS添加到标准的基于MC3的四组分LNP制剂（PS-LNP）中，以促进免疫细胞的细胞摄取，超越了当今常用的电荷驱动靶向原理。结果，PS-LNP在IV给药后在淋巴结和脾脏中进行有效的蛋白表达。PS-LNP的体外和体内表征证明了单核细胞/巨噬细胞介导的SLOs靶向递送机制。
Secondary lymphoid organs (SLOs) are an important target for mRNA delivery in various applications. While the current delivery method relies on the drainage of nanoparticles to lymph nodes by intramuscular (IM) or subcutaneous (SC) injections, an efficient mRNA delivery carrier for SLOs-targeting delivery by systemic administration (IV) is highly desirable but yet to be available. In this study, we developed an efficient SLOs-targeting carrier using phosphatidylserine (PS), a well-known signaling molecule that promotes the endocytic activity of phagocytes and cellular entry of enveloped viruses. We adopted these biomimetic strategies and added PS into the standard four-component MC3based LNP formulation (PS-LNP) to facilitate the cellular uptake of immune cells beyond the charge-driven targeting principle commonly used today. As a result, PS-LNP performed efficient protein expression in both lymph nodes and the spleen after IV administration. In vitro and in vivo characterizations on PS-LNP demonstrated a monocyte/macrophage-mediated SLOs-targeting delivery mechanism.