Development of amino acid-based cationic lipid nanoparticles specialized for cytosolic gene delivery

开发专门用于胞质基因传递的基于氨基酸的阳离子脂质纳米粒子

• 批准号: 19K20700
• 负责人: 李 天舒
• 金额: $ 2.66万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19K20700/
• 关键词: Cationic lipid; Lipid nanoparticle; Microfluidic preparation; Immunostimulation; Lipid nanoparticles; Cationic liposomes; Gene delivery; Immune stimulation; T cell activation; Calcium mobilization; lipid nanoparticle; plasmid DNA; 3D spheroid

The effect of lipid nanoparticle (LNP) composition on pDNA transfection and cytotoxicity had been investigated using lysine type cationic lipids K3C16 as the main component. Various types and ratios of helper lipids were challenged and it was found that 1.5mol% PEG2000 and 10mol% DOPE endowed the best transfection efficiency among all the tested groups without significant cytotoxicity in comparison to Lipofectamin3000. In addition, microfluidic method using SHM for LNP preparation had been successfully achieved, which allowed trace amount fabrication with fine tuned size around 100 nm and a better monodispersity than conventional bulk method.In the study of arginine type lipids, the lipid structure effect on T cell activation was disclosed and one academic paper was published.

以赖氨酸型阳离子脂质K3C16为主要成分，研究了脂质纳米粒（LNP）组成对pDNA转染和细胞毒性的影响。对不同类型和比例的辅助脂质进行挑战，发现1.5mol%PEG 2000和10mol%DOPE在所有测试组中赋予最佳转染效率，与Lipofectamin3000相比没有显著的细胞毒性。此外，还成功实现了基于SHM的微流控方法制备LNP，实现了100 nm左右的微量制备，单分散性优于传统的本体法。在精氨酸类脂质的研究中，揭示了脂质结构对T细胞活化的影响，并发表了一篇学术论文。

项目成果

Arginine-based cationic liposomes accelerate T cell activation and differentiation in vitro

• DOI: 10.1016/j.ijpharm.2022.121917
• 发表时间: 2022-07-25
• 期刊: INTERNATIONAL JOURNAL OF PHARMACEUTICS
• 影响因子: 5.8
• 作者: Li, Tianshu;Tolksdorf, Felix;Takeoka, Shinji
• 通讯作者: Takeoka, Shinji

University of Bonn(ドイツ)

波恩大学（德国）

Evaluation of Cationic Liposomes on Inducing Calcium Mobilization in THP-1 Cells

阳离子脂质体诱导 THP-1 细胞钙动员的评价

• 发表时间: 2021
• 作者: Aya Kitanaka;Tianshu Li;Shinji Takeoka
• 通讯作者: Shinji Takeoka

Preliminary study on the in vitro pre-activation of T cells by arginine-based cationic liposomes

精氨酸阳离子脂质体体外预激活T细胞的初步研究

• 发表时间: 2021
• 作者: Tianshu Li;Shinji Takeoka
• 通讯作者: Shinji Takeoka

Lipid structure effect on the interaction of nanoparticles with macrophages

脂质结构对纳米颗粒与巨噬细胞相互作用的影响

• 发表时间: 2019
• 作者: 寺井崇人;梨本裕司;伊野浩介;西山功一;横川隆司;三浦岳;珠玖仁;Tianshu Li
• 通讯作者: Tianshu Li