A manganese (II)-based coordinative dendrimer with robust efficiency in intracellular peptide delivery

Peptides have gained increasing interests as drug candidates in modern pharmaceutical industry, however, the development of peptide drugs acting on intracellular targets is limited due to their membrane impermeability. Here, we reported the use of metal-terpyridine based coordinative dendrimer for cytosolic peptide delivery. Among the investigated transition metal ions, Mn²⁺-coordinated polymer showed the highest delivery efficiency due to balanced peptide binding and release. It showed robust efficiency in the delivery of peptides with different charge property and hydrophobicity into various primary cells. The efficiency of Mn²⁺-terpyridine based polymer is superior to cell penetrating peptides such as oligoarginines. The material also delivered an autophagy-inducing peptide derived from Beclin-1 into cells and efficiently induced autophagy in the cells. This study provides a promising alternative to cell penetrating peptides for cytosolic peptide delivery.