Clodronate Liposomes氯膦酸盐脂质体清除肝脏Kuffer巨噬细胞文献参考解决方案

中文摘要：

脂质纳米颗粒 （LNP） 是基于 mRNA 的疗法的非病毒递送载体。人们在优化可电离脂质 （IL） 结构方面投入了大量精力，该结构包含与脂质尾部共轭的胺核，因为微小的分子调整会导致所得 LNP 的整体功效发生重大变化。然而，尽管取得了一些进展，但 LNP 递送的一个主要障碍是内体逃逸。在这里，我们开发了一个平台来合成一类改善内体逃逸的分支 IL。与非支链脂质相比，这些化合物包含末端支链基团，可增加肝脏 mRNA 和核糖核蛋白复合物的递送和基因编辑效率以及 T 细胞转染。通过一系列互补实验，我们确定我们的脂质结构诱导更大的内体渗透和破坏。这项工作提供了一种为 mRNA 和蛋白质递送生成一类 IL 的方案。

英文摘要：

Lipid nanoparticles (LNPs) are the preeminent non-viral drug delivery vehicle for mRNA-based therapies. Immense effort has been placed on optimizing the ionizable lipid (IL) structure, which contains an amine core conjugated to lipid tails, as small molecular adjustments can result in substantial changes in the overall efficacy of the resulting LNPs. However, despite some advancements, a major barrier for LNP delivery is endosomal escape. Here, we develop a platform for synthesizing a class of branched ILs that improve endosomal escape. These compounds incorporate terminally branched groups that increase hepatic mRNA and ribonucleoprotein complex delivery and gene editing efficiency as well as T cell transfection compared to non-branched lipids. Through an array of complementary experiments, we determine that our lipid architecture induces greater endosomal penetration and disruption. This work provides a scheme to generate a class of ILs for both mRNA and protein delivery.

论文信息：

论文题目：

Branched endosomal disruptor (BEND) lipids mediate delivery of mRNA and CRISPR-Cas9 ribonucleoprotein

complex for hepatic gene editing and T cell engineering

期刊名称：Nature Communications

时间期卷：volume 16, Article number: 996 (2025)

在线时间：2025年1月24日

DOI：doi.org/10.1038/s41467-024-55137-6

产品信息：

货号：CP-005-005

规格：5ml+5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes and Control Liposomes

办事处：Target Technology（靶点科技）

Clodronate Liposomes氯膦酸盐脂质体助力脂质纳米颗粒 （LNP）递送研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：

Clodronate Liposomes氯膦酸盐脂质体清除肝脏Kuffer巨噬细胞文献参考解决方案

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

Kupffer cell knockdown

Kupffer cells from C57BL/6J female mice, 6–8 weeks old, were depleted by administering 0.2 mL of clodronate liposomes (Liposoma, Amsterdam, Netherlands) at a dose of 5 mg/mL via the lateral tail vein. After 24 h, the mice were reinjected via the lateral tail vein with LNPs encapsulated FLuc at a dose of 0.1 mg/kg. After 12 h, liver luminescence was quantified as described above.