Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除肝臟Kuffer巨噬細(xì)胞文獻(xiàn)參考解決方案

中文摘要：

脂質(zhì)納米顆粒 （LNP） 是基于 mRNA 的療法的非病毒遞送載體。人們?cè)趦?yōu)化可電離脂質(zhì) （IL） 結(jié)構(gòu)方面投入了大量精力，該結(jié)構(gòu)包含與脂質(zhì)尾部共軛的胺核，因?yàn)槲⑿〉姆肿诱{(diào)整會(huì)導(dǎo)致所得 LNP 的整體功效發(fā)生重大變化。然而，盡管取得了一些進(jìn)展，但 LNP 遞送的一個(gè)主要障礙是內(nèi)體逃逸。在這里，我們開發(fā)了一個(gè)平臺(tái)來合成一類改善內(nèi)體逃逸的分支 IL。與非支鏈脂質(zhì)相比，這些化合物包含末端支鏈基團(tuán)，可增加肝臟 mRNA 和核糖核蛋白復(fù)合物的遞送和基因編輯效率以及 T 細(xì)胞轉(zhuǎn)染。通過一系列互補(bǔ)實(shí)驗(yàn)，我們確定我們的脂質(zhì)結(jié)構(gòu)誘導(dǎo)更大的內(nèi)體滲透和破壞。這項(xiàng)工作提供了一種為 mRNA 和蛋白質(zhì)遞送生成一類 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.

論文信息：

論文題目：

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

complex for hepatic gene editing and T cell engineering

期刊名稱：Nature Communications

時(shí)間期卷：volume 16, Article number: 996 (2025)

在線時(shí)間：2025年1月24日

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

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點(diǎn)科技）

Clodronate Liposomes氯膦酸鹽脂質(zhì)體助力脂質(zhì)納米顆粒 （LNP）遞送研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除肝臟Kuffer巨噬細(xì)胞文獻(xiàn)參考解決方案

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

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.