基于非基因工程技术的细胞表面修饰策略研究进展

doi:10.19586/j.2095-2341.2024.0002

生物技术进展 ›› 2024, Vol. 14 ›› Issue (4): 555-565.DOI: 10.19586/j.2095-2341.2024.0002

• 进展评述 • 上一篇

基于非基因工程技术的细胞表面修饰策略研究进展

毕瑞¹(), 武江波², 马春靖¹

^1.唐山市人民医院药学部，河北唐山 063000
^2.河北省唐山市市场监督管理局，药品不良反应监测中心，河北唐山 063000

收稿日期:2024-01-09 接受日期:2024-05-30 出版日期:2024-07-25 发布日期:2024-08-07
作者简介:毕瑞 E-mail: 14901932@qq.com
基金资助:
河北省唐山市科技计划项目(14130256a);河北省药学会临床药学专项科研项目(YX201506)

Research Progress on Cell Surface Modification Strategies Based on Non-genetic Engineering Technologies

Rui BI¹(), Jiangbo WU², Chunjing MA¹

^1.Department of Pharmacy，Tangshan People's Hospital，Hebei Tangshan 063000，China
^2.Adverse Drug Reaction Monitoring Center，Market Supervision Administration of Tangshan，Hebei Tangshan 063000，China

Received:2024-01-09 Accepted:2024-05-30 Online:2024-07-25 Published:2024-08-07

摘要/Abstract

摘要：

细胞表面成分与结构在维持细胞内代谢环境稳定、控制细胞内外物质交换和促进细胞间通讯方面发挥着至关重要的作用，因此，调节或改变细胞表面成分对研究细胞命运具有重要意义。基因工程是目前调节细胞表面成分最常用的技术，但是由于这种方法具有转染效率低、存在突变风险等问题，其应用范围仍然有限。相比之下，近些年发展起来的多种非基因工程细胞表面修饰技术，具有简便、易操作、适用范围广等优势，为调控细胞生命活动、赋予细胞新的性质和功能提供了更多新的选择，因而其在基础生物学研究和新药研发中具有广泛应用前景。对目前非基因工程技术的原理、特点以及在细胞治疗领域的应用等进行了综述和讨论，期望有助于深入了解这一新技术及其在生物医学领域中的应用。

关键词: 非基因工程, 细胞表面修饰技术, 细胞治疗, 新药研发

Abstract:

The cell surface plays a crucial role in maintaining a stable intracellular metabolic environment， controlling the exchange of substances inside and outside the cell， and facilitating intercellular communication. Therefore， the regulation or alteration of cell surface components is of significant importance in studying cellular fate. While genetic engineering remains the most commonly used technique for modulating cell surface components， its application is limited due to challenges such as low transfection efficiency and the risk of mutations. In contrast， various non-genetic engineering strategies developed in recent years offer new alternatives for regulating cellular activities， imparting cell with novel properties， and enhancing functionalities without the complexities associated with genetic manipulations. These non-genetic engineering approaches are characterized by their simplicity， ease of operation， and broad applicability， making them promising in fundamental biological research and pharmaceutical development. This paper provided a comprehensive review and discussion of the principles and characteristics of current non-genetic engineering strategies for cell surface modification， along with their applications in the field of cell therapy， aiming to offer insights into these strategies， develop new methodologies， and expand their biomedical applications.

Key words: non-genetic engineering, cell surface modification technology, cell therapy, drug development

中图分类号:

Q953

毕瑞, 武江波, 马春靖. 基于非基因工程技术的细胞表面修饰策略研究进展[J]. 生物技术进展, 2024, 14(4): 555-565.

Rui BI, Jiangbo WU, Chunjing MA. Research Progress on Cell Surface Modification Strategies Based on Non-genetic Engineering Technologies[J]. Current Biotechnology, 2024, 14(4): 555-565.

图/表 5

图1 基于氨基的修饰策略与应用A：细胞表面功能性基团示意图[9]；B：制备金属生物复合材料示意图[11]；C：细胞亮氨酸拉链装饰示意图[12]；SH—疏基

Fig. 1 Amine-based chemical modification strategies and applications

图2 基于巯基的修饰策略与应用A：PEG修饰纳米颗粒与红细胞表面巯基的共价偶联及其被巨噬细胞吞噬示意图[23]；B：PDP介导的二硫键形成反应用于细胞表面装载脂质体颗粒示意图[26]；C：NEs@STING-Mal-NP的制备和抗肿瘤原理示意图[25]。PLGA—聚乳酸-聚甘醇酸；PTX—紫杉醇；DSPE-PEG—1,2-二硬脂酰基-sn-丙三基-3-磷脂酰乙醇胺-聚乙二醇；Mal—马来酰亚胺；SLN—固体脂质纳米粒子；TAM—肿瘤相关巨噬细胞；MDSC—髓源性抑制性细胞；TCEP—三(2-羧乙基)膦；TNBC—三阴性乳腺癌；ICIs(aPD1）—免疫检查点抑制剂(抗程序性细胞死亡蛋白1)。

Fig. 2 Thiol-based chemical modification strategies and applications

图3 代谢寡糖工程的应用A：造血干细胞通与血小板组装后辅助aPD-1递送示意图[36]；B：应用代谢寡糖工程和双正交化学诱导细胞间粘附示意图[30]；C：应用代谢标记法和生物正交点击反应将炔烃和PEG修饰的β-CD与细胞膜结合示意图[37]。SA—唾液酸；PMP—血小板微颗粒；TCR—T细胞受体；MCH—主要组织相容性复合体；DBCO—二苯并环辛炔；TCO—反式环辛烯；GalNAz—N-叠氮乙酰半乳糖胺；UDP-GalNAz—尿苷5'-二磷酸-N-叠氮乙酰半乳糖胺二钠盐。

Fig. 3 The application of metabolic oligosaccharide engineering.

图4 酶修饰的应用策略A：岩藻糖基转移酶辅助下将抗体偶联到细胞表面示意图[48]；B：酪氨酸标记的纳米体在酪氨酸酶辅助下将蛋白质附着到细胞上的示意图[49]；C：Herceptin-NK-92MI共轭物特异性结合HER2阳性癌细胞示意图[48]；D：在Sortase A酶辅助下用携带GGG的抗原肽标记细胞的示意图[43]。ACC—抗体细胞偶联物；GDP—二磷酸鸟苷；GF-IgG—抗体与二磷酸鸟苷-岩藻糖偶联物；α1,3 FucT—α1,3岩藻糖基转移酶；abTRY—双孢蘑菇的酪氨酸酶；LPET—氨基酸序列，包括leucine（亮氨酸）、proline（脯氨酸）、glutamic acid（谷氨酸）、threonine（苏氨酸）；GGG—三个甘氨酸。

Fig. 4 Application strategies of enzymatic modification

图5 基于疏水性插入修饰策略与应用A：基于疏水性插入策略下的细胞融合[63]；B~C：DNAzyme与底物在特定金属离子辅助下实现了细胞之间的组装和解离[64]；D：将PD-L1分子固定在靶向细胞膜上的示意图[65]

Fig. 5 Hydrophobic insertion-based modification strategies and applications

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基于非基因工程技术的细胞表面修饰策略研究进展

Research Progress on Cell Surface Modification Strategies Based on Non-genetic Engineering Technologies

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