Citation: Shuwen Guo, Haipeng Xu, Zijun Cheng, Leyong Wang, Peng Yang, Ruibing Wang. Efficient cytosolic delivery of protein by preorganized amidiniums on pillar[5]arene[J]. Chinese Chemical Letters, ;2025, 36(10): 111022. doi: 10.1016/j.cclet.2025.111022 shu

Efficient cytosolic delivery of protein by preorganized amidiniums on pillar[5]arene

Shuwen Guo ^{a, *,} ,
Haipeng Xu ^a ,
Zijun Cheng ^a ,
Leyong Wang ^b ,
Peng Yang ^{a, *,} ,
Ruibing Wang ^{c, *,}

a.
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China
b.
Key Laboratory of Mesoscopic Chemistry of MOE, Jiangsu Key Laboratory of Advanced Oganic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
c.
State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau Taipa, Macau 999078, China

guoshuwen@snnu.edu.cn

yangpeng@snnu.edu.cn

rwang@um.edu.mo

Received Date: 17 December 2024
Revised Date: 25 February 2025
Accepted Date: 28 February 2025
Available Online: 4 March 2025

Figures(6)

Intracellular protein delivery is vital for the development of therapeutic proteins that act on intracellular targets. Although numerous carriers based on polymers and nanomaterials have been reported to facilitate cellular internalization of membrane impermeable proteins, it is still a great challenge to intracellularly deliver proteins with different sizes and isoelectric points through small molecule-based protein carrier. Herein, amidinium functionalized pillar[5]arene (AP5) was used as a small molecular carrier to facilitate intracellular delivery of proteins with different sizes and isoelectric points. The densely preorganized amidinium groups on pillar[5]arene skeleton could not only glue proteins together to form AP5@protein complex through multiple salt-bridges, but also promote cellular internalization AP5@protein complex. The bioactivities of the internalized proteins were well-maintained. This study provides a novel, versatile and macrocyclic-molecule based intracellular protein delivery carrier through the preorganization of amidiniums on pillar[5]arene.
- Proteins delivery,
- Pillar[5]arene,
- Amidinium,
- Self-assembly,
- Preorganization
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