Development of a novel cholesterol tag-based system for trans-membrane transport of protein drugs

被引:0
作者
Zhao, Pengfei [1 ,3 ,4 ]
Song, Shuo [5 ]
He, Zhuojun [1 ,2 ,3 ]
Dai, Guiqin [1 ,3 ]
Liu, Deliang [1 ,3 ]
Shen, Jiayin [1 ,3 ]
Asakawa, Tetsuya [1 ]
Zheng, Mingbin [1 ,2 ,3 ,5 ]
Lu, Hongzhou [1 ,3 ,6 ]
机构
[1] Third Peoples Hosp Shenzhen, Inst Neurol, Natl Clin Res Ctr Infect Dis, 29 Bulan Rd, Shenzhen 518112, Guangdong, Peoples R China
[2] Guangdong Med Univ, Key Lab Nanomed, Dongguan, Guangdong, Peoples R China
[3] Third Peoples Hosp Shenzhen, Inst Hepatol, Natl Clin Res Ctr Infect Dis, Shenzhen Clin Med Res Ctr TB, Shenzhen, Guangdong, Peoples R China
[4] Shenzhen Univ, Coll Phys & Optoelect Engn, Shenzhen Key Lab Photon & Biophoton, Key Lab Optoelect Devices & Syst,Minist Educ & Gua, Shenzhen, Peoples R China
[5] Shenzhen Samii Med Ctr, Shenzhen, Guangdong, Peoples R China
[6] Third Peoples Hosp Shenzhen, Natl Clin Res Ctr Infect Dis, Dept Infect Dis, 29 Bulan Rd, Shenzhen 518112, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
protein drug; cell membrane; transmembrane transport; cholesterol tag; intraparticle delivery; DELIVERY; PLATFORM; DISEASE;
D O I
10.5582/bst.2023.01285
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The main technological difficulties of developing an intracellular (transmembrane) transport system for protein drugs lie in two points: i) overcoming the barriers in the cellular membrane, and ii) loading enough protein drugs, and particularly high-dose proteins, into particles. To address these two technological problems, we recently developed a novel cholesterol tag (C-Tag)-based transmembrane transport system. This pilot study found that the C-Tag dramatically improved the cellular uptake of Fab (902-fold, vs. Fab alone) into living cells, indicating that it successfully achieved transmembrane transport. Moreover, C-Tag-mediated membrane transport was verified using micron-scale large unilamellar vesicles (LUVs, approximately 1.5 mu m)-based particles. The C-Tagged Fab was able to permeate the liposomal bilayer and it greatly enhanced (a 10.1-fold increase vs. Fab alone) internalization of proteins into the LUV-based particles, indicating that the C-Tag loaded enough proteins into particles for use of high-dose proteins. Accordingly, we established a novel C-Tag-based transport system that has overcome the known technological difficulties of protein transmembrane delivery, and this might be a useful technology for drug development in the future.
引用
收藏
页码:503 / 507
页数:5
相关论文
共 20 条
[1]   Effects and mechanisms of microenvironmental acidosis on osteoclast biology [J].
Gong, Shuwei ;
Ma, Jianxiong ;
Tian, Aixian ;
Lang, Shuang ;
Luo, Zhiheng ;
Ma, Xinlong .
BIOSCIENCE TRENDS, 2022, 16 (01) :58-72
[2]   Polymeric protagonists for biological processes [J].
Gudinas, Alana P. ;
Mai, Danielle J. .
NATURE CHEMISTRY, 2023, 15 (06) :751-752
[3]   Monitoring protein conformational changes using fluorescent nanoantennas [J].
Harroun, Scott G. ;
Lauzon, Dominic ;
Ebert, Maximilian C. C. J. C. ;
Desrosiers, Arnaud ;
Wang, Xiaomeng ;
Vallee-Belisle, Alexis .
NATURE METHODS, 2022, 19 (01) :71-+
[4]   Role of key amino acids in the transmembrane domain of the Newcastle disease virus fusion protein [J].
Huang, Yanan ;
Liu, Yaqing ;
Li, Yanguo ;
Liu, Ying ;
Zhang, Chi ;
Wen, Hongling ;
Zhao, Li ;
Song, Yanyan ;
Wang, Liyang ;
Wang, Zhiyu .
BIOSCIENCE TRENDS, 2021, 15 (01) :16-23
[5]   Engineering precision nanoparticles for drug delivery [J].
Mitchell, Michael J. ;
Billingsley, Margaret M. ;
Haley, Rebecca M. ;
Wechsler, Marissa E. ;
Peppas, Nicholas A. ;
Langer, Robert .
NATURE REVIEWS DRUG DISCOVERY, 2021, 20 (02) :101-124
[6]   Real-Time Monitoring of a Protein Biomarker [J].
Parolo, Claudio ;
Idili, Andrea ;
Ortega, Gabriel ;
Csordas, Andrew ;
Hsu, Alex ;
Arroyo-Curras, Netzahualcoyotl ;
Yang, Qin ;
Ferguson, Brian Scott ;
Wang, Jinpeng ;
Plaxco, Kevin W. .
ACS SENSORS, 2020, 5 (07) :1877-1881
[7]   Can kynurenine pathway be considered as a next-generation therapeutic target for Parkinson's disease? An update information [J].
Qin, Wei ;
Shi, Yirong ;
Chen, Weimei ;
Jia, Xiaokang ;
Asakawa, Tetsuya .
BIOSCIENCE TRENDS, 2022, 16 (04) :249-256
[8]  
Qin Y, 2023, ADV MATER
[9]   Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases [J].
Raman, Vishnu ;
Van Dessel, Nele ;
Hall, Christopher L. ;
Wetherby, Victoria E. ;
Whitney, Samantha A. ;
Kolewe, Emily L. ;
Bloom, Shoshana M. K. ;
Sharma, Abhinav ;
Hardy, Jeanne A. ;
Bollen, Mathieu ;
Van Eynde, Aleyde ;
Forbes, Neil S. .
NATURE COMMUNICATIONS, 2021, 12 (01)
[10]   Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells [J].
Shalek, Alex K. ;
Robinson, Jacob T. ;
Karp, Ethan S. ;
Lee, Jin Seok ;
Ahn, Dae-Ro ;
Yoon, Myung-Han ;
Sutton, Amy ;
Jorgolli, Marsela ;
Gertner, Rona S. ;
Gujral, Taranjit S. ;
MacBeath, Gavin ;
Yang, Eun Gyeong ;
Park, Hongkun .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (05) :1870-1875