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A Coordinative Dendrimer Achieves Excellent Efficiency in Cytosolic Protein and Peptide Delivery
Author(s) -
Ren Lanfang,
Lv Jia,
Wang Hui,
Cheng Yiyun
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201914970
Subject(s) - cytosol , dendrimer , internalization , chemistry , biophysics , intracellular , isoelectric point , polymer , peptide , combinatorial chemistry , ionic bonding , drug delivery , biochemistry , ion , organic chemistry , biology , receptor , enzyme
Cytosolic protein delivery is a prerequisite for the development of protein therapeutics that act on intracellular targets. Proteins are generally membrane‐impermeable and thus need a carrier such as a polymer to facilitate their internalization. However, the efficient binding of proteins with different isoelectric points to polymeric carriers is challenging. In this study, we designed a coordinative dendrimer to solve this problem. The dendrimers modified with dipicolylamine/zinc(II) complex were capable of binding proteins through a combination of ionic and coordination interactions. The best polymer efficiently delivered 30 cargo proteins and peptides into the cytosol, while maintaining their bioactivity after intracellular release. The removal or replacement of zinc ions in the polymer with other transition‐metal ions lead to significantly decreased efficiency in cytosolic protein delivery. This study provides a new strategy to develop robust and efficient polymers for cytosolic protein delivery.