Ligand-free hepatocyte-targeting of nanomedicines by selective stealth coating of liver reticuloendothelial system scavenger cells

通过肝网状内皮系统清道夫细胞的选择性隐形涂层实现纳米药物的无配体肝细胞靶向

• 批准号: 21K18062
• 负责人: ディリサラ アンジャネユル
• 金额: $ 2.91万
• 依托单位: Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K18062/
• 关键词: Liver stealth coating; Hepatocyte targeting; Gene delivery; Hepatocytes; Genome editing; CRISPR/Cas9; Gene drugs

The luciferase-encoding mRNA encapsulated cationic (lipid to mRNA ratio 5:1, charge +52 mV, size 155 nm) and anionic (lipid to mRNA ratio 1:2, charge -30 mV, size 221 nm) mRNA-lipoplexes were prepared by different coating amounts of the mRNA onto liposomes composed of DOTMA and DOPE. Prior stealth coating of the liver sinusoidal RES wall with two-arm-PEG-Oligo(L-Lysine) substantially enhanced the luciferase expression (14.1-fold increase) of anionic liposome in the liver compared to without liver coating. Similarly, PEG coating to the liver scavenger cell wall augmented the luciferase expression in the liver up to 3.6-fold compared to without coating. Based on these results, the applicant will choose anionic mRNA-lipoplex for future liver-directed therapeutic applications.

将编码荧光素酶的mRNA包被阳离子（脂质与mRNA之比为5:1，电荷为+52 mV，尺寸为155 nm）和阴离子（脂质与mRNA之比为1:2，电荷为-30 mV，尺寸为221 nm） mRNA-脂质体，并将其包被不同量的mRNA包被在由DOTMA和DOPE组成的脂质体上。先前用双臂peg - oligo （l -赖氨酸）隐形覆盖肝窦RES壁，与未覆盖肝壁相比，肝脏中阴离子脂质体荧光素酶的表达显著增强（增加14.1倍）。同样，与未涂膜相比，肝脏清道夫细胞壁上的PEG涂层可使肝脏中荧光素酶的表达增加3.6倍。基于这些结果，申请人将选择阴离子mrna -脂质体用于未来的肝脏定向治疗应用。

项目成果

複合体、医薬、癌治療剤、キット及び結合体

复合物、药物、癌症治疗剂、试剂盒和缀合物

• 发表时间: 2021

Bridging mRNA and polycation using RNA oligonucleotide derivatives improves the robustness of polyplex micelle for efficient mRNA delivery.

使用 RNA 寡核苷酸衍生物桥接 mRNA 和聚阳离子可提高聚合物胶束的稳健性，以实现有效的 mRNA 递送。

• DOI: 10.1002/adhm.202102016
• 发表时间: 2021
• 期刊: Advanced Healthcare Materials,
• 作者: N. Yoshinaga;S. Uchida;A. Dirisala;M. Naito;K. Koji;K. Osada;H. Cabral;K. Kataoka,
• 通讯作者: K. Kataoka,

Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer

• DOI: 10.1002/adma.202105254
• 发表时间: 2021-10-07
• 期刊: ADVANCED MATERIALS
• 影响因子: 29.4
• 作者: Li, Junjie;Ge, Zhishen;Kataoka, Kazunori
• 通讯作者: Kataoka, Kazunori

Effective mRNA Protection by Poly(l-ornithine) Synergizes with Endosomal Escape Functionality of a Charge-Conversion Polymer toward Maximizing mRNA Introduction Efficiency

• DOI: 10.1002/marc.202100754
• 发表时间: 2022-03-18
• 期刊: MACROMOLECULAR RAPID COMMUNICATIONS
• 影响因子: 4.6
• 作者: Dirisala, Anjaneyulu;Uchida, Satoshi;Kataoka, Kazunori
• 通讯作者: Kataoka, Kazunori