制备干扰素脂质体使小胶质细胞维持M1表型

doi:10.5246/jcps.2019.07.046

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (7): 476-483.DOI: 10.5246/jcps.2019.07.046

制备干扰素脂质体使小胶质细胞维持M1表型

杜祎甜^1,2, 张泸^1,2, 詹颖^1,2, 柴新宇^1,2, 李锴森^1,2, 齐宪荣^1,2*

1. 北京大学医学部药学院药剂学系, 北京 100191
2. 北京大学医学部分子药剂学与新释药系统北京市重点实验室, 北京 100191

收稿日期:2019-05-06 修回日期:2019-05-27 出版日期:2019-07-31 发布日期:2019-06-13
通讯作者: Tel.: +86+010-82801584, E-mail: qixr@bjmu.edu.cn
基金资助:
National Nature Science Foundation of China (Grant No. 81673365 and 81473156).

Interferon-liposomes prepared to make macroglia maintain M1 phenotype

Yitian Du^1,2, Lu Zhang^1,2, Yin Zhan^1,2, Xinyu Chai^1,2, Kaisen Li^1,2, Xianrong Qi^1,2*

1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2019-05-06 Revised:2019-05-27 Online:2019-07-31 Published:2019-06-13
Contact: Tel.: +86+010-82801584, E-mail: qixr@bjmu.edu.cn
Supported by:
National Nature Science Foundation of China (Grant No. 81673365 and 81473156).

摘要/Abstract

摘要：

小胶质细胞是一种只存在于中枢神经系统中重要的巨噬细胞。它在脑胶质瘤进展中可以被激活为M2抗炎表型进而促进肿瘤的生长。干扰素-γ是胶质瘤微环境中一种重要的免疫调节因子,它可以将小胶质细胞激活为M1促炎表型,从而增强抗肿瘤免疫并导致肿瘤生长抑制。因此,我们利用干扰素-γ使小胶质细胞维持M1表型,有望实现抗肿瘤免疫的胶质瘤治疗。我们制备了干扰素脂质体以保护干扰素-γ不被清除。实验证明,干扰素脂质体具有很强的被小胶质细胞吞噬并蓄积于细胞内的能力,可以长期发挥药效。另外,干扰素脂质体可以使小胶质细胞维持M1表型,同时不影响细胞活性。这些研究成果将为增强胶质瘤免疫疗法提供新的机遇。

关键词: 干扰素, 脂质体, 小胶质细胞, 药物递送

Abstract:

Macroglia is a crucial macrophage only existing in the central nervous system. During the development of glioma, it can be activated as M2 anti-inflammatory type to promote glioma growth. Interferon-γ (IFN-γ) is an important immunomodulator inglioma microenvironment, which can also activate macroglia as M1 pro-inflammatory type to enhance anti-tumor immune responseand lead to inhibition of glioma growth. Therefore, we utilized IFN-γ to make macroglia maintain M1 phenotype, so that prospectively achieving anti-tumor immunity for glioma therapy. We prepared interferon-γ-liposomes (IFN-Lp) to protect IFN-γ from elimination. IFN-Lp was proved to have strong capability to be phagocytosed and accumulate in macroglia (BV2 cells) to achieve long-term effect. In addition, IFN-Lp could allow BV2 cells to maintain M1 phenotype, showing no impact on its cell viability. These findings will offer new opportunities to achieve enhanced immunotherapy of glioma.

Key words: Interferon-γ, Liposomes, Microglia, Drug delivery

中图分类号:

R943

Supporting:

杜祎甜, 张泸, 詹颖, 柴新宇, 李锴森, 齐宪荣. 制备干扰素脂质体使小胶质细胞维持M1表型[J]. 中国药学(英文版), 2019, 28(7): 476-483.

Yitian Du, Lu Zhang, Yin Zhan, Xinyu Chai, Kaisen Li, Xianrong Qi. Interferon-liposomes prepared to make macroglia maintain M1 phenotype[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(7): 476-483.

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制备干扰素脂质体使小胶质细胞维持M1表型

Interferon-liposomes prepared to make macroglia maintain M1 phenotype

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