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首页> 外文期刊>Biomaterials Science >Cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reactions
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Cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reactions

机译：通过代谢甘油糖细胞蛋白递送和生物正交咔哒反应

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摘要

Cytosolic protein delivery holds great potential for the development of protein-based biotechnologies and therapeutics. Currently, cytosolic protein delivery is mainly achieved with the assistance of various carriers. Herein, we present a universal and effective strategy for carrier-free cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reactions. Ac(4)ManNAz (AAM), an azido-modified N-acetylmannosamine analogue, was first employed to label tumor cell surfaces with abundant azido groups via glycometabolism. Then, proteins including RNase A, cytochrome C (Cyt C), and bovine serum albumin (BSA) were covalently modified with dibenzocyclooctyne (DBCO). Based on the highly efficient bioorthogonal click reactions between DBCO and azido, DBCO-modified proteins could be efficiently internalized by azido-labeled cancer cells. RNase A-DBCO could largely maintain its enzymatic activity and, thus, led to notable anti-tumor efficacy in HeLa and B16F10 cells in vitro and in B16F10 xenograft tumors in vivo. This study therefore provides a simple and powerful approach for carrier-free protein delivery and would have broad applicability in anti-tumor protein therapy.
机译：细胞溶质蛋白质递送占蛋白质的生物技术和治疗方法的巨大潜力。目前，在各种载体的帮助下主要实现了细胞溶蛋白递送。在此，我们介绍了通过代谢甘油糖细胞和生物正交咔哒反应的载体自由胞质蛋白递送的普遍性和有效的策略。 AC（4）Mannaz（AAM），首先使用含有含有丰富的Azido基团的肿瘤细胞表面与含有含糖蛋白酶的肿瘤细胞表面标记。然后，用二苯并苯并辛（DBCO）共价修饰包括RNase A，细胞色素C（CYT C）和牛血清白蛋白（BSA）的蛋白质。基于DBCO和Azido之间的高效生物正交鼠标反应，DBCO改性蛋白质可以通过氮杂-标记的癌细胞有效地内化。 RNase A-DBCO可以在很大程度上维持其酶活性，因此在体内和B16F10异种移植肿瘤中导致HeLa和B16F10细胞中值得注意的抗肿瘤效果。因此，该研究为无载体蛋白质递送提供了一种简单且强大的方法，并在抗肿瘤蛋白质治疗中具有广泛的适用性。

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  • 来源
    《Biomaterials Science》 |2021年第13期|共9页
  • 作者

    Zhao Ziyin; Zhang Zhimin; Duan Shanzhou; Liu Xun; Zhou Renxiang; Hou Mengying; Sang Yonghua; Zhu Rongying; Yin Lichen;

  • 作者单位

    Soochow Univ Collaborat Innovat Suzhou Nano Sci &

    Technol Jiangsu Key Lab Carbon Based Funct Mat &

    Devices Inst Funct Nano &

    Soft Mat FUNSOM Suzhou 215123 Peoples R China;

    Soochow Univ Collaborat Innovat Suzhou Nano Sci &

    Technol Jiangsu Key Lab Carbon Based Funct Mat &

    Devices Inst Funct Nano &

    Soft Mat FUNSOM Suzhou 215123 Peoples R China;

    Soochow Univ Affiliated Hosp 2 Suzhou Key Lab Thorac Oncol Dept Thorac Surg Suzhou 215004 Peoples R China;

    Soochow Univ Collaborat Innovat Suzhou Nano Sci &

    Technol Jiangsu Key Lab Carbon Based Funct Mat &

    Devices Inst Funct Nano &

    Soft Mat FUNSOM Suzhou 215123 Peoples R China;

    Soochow Univ Collaborat Innovat Suzhou Nano Sci &

    Technol Jiangsu Key Lab Carbon Based Funct Mat &

    Devices Inst Funct Nano &

    Soft Mat FUNSOM Suzhou 215123 Peoples R China;

    Soochow Univ Collaborat Innovat Suzhou Nano Sci &

    Technol Jiangsu Key Lab Carbon Based Funct Mat &

    Devices Inst Funct Nano &

    Soft Mat FUNSOM Suzhou 215123 Peoples R China;

    Soochow Univ Affiliated Hosp 2 Suzhou Key Lab Thorac Oncol Dept Thorac Surg Suzhou 215004 Peoples R China;

    Soochow Univ Affiliated Hosp 2 Suzhou Key Lab Thorac Oncol Dept Thorac Surg Suzhou 215004 Peoples R China;

    Soochow Univ Collaborat Innovat Suzhou Nano Sci &

    Technol Jiangsu Key Lab Carbon Based Funct Mat &

    Devices Inst Funct Nano &

    Soft Mat FUNSOM Suzhou 215123 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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