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 cel...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.展开更多
基金the financial support from the National Natural Science Foundation of China(No.22101310)Fundamental Research Funds for the Central Universities(No.GK202207013)NJU International Fellowship program。
文摘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.
