pH-Activatable cell penetrating peptide dimers for potent delivery of anticancer drug to triple-negative breast cancer

We developed a pH-activatable cell-penetrating peptide dimer LH2 with histidine residues, which can penetrate cells, specifically in weak acidic conditions, even at few tens of nanomolar concentrations. LH2 effectively delivered paclitaxel into triple-negative breast cancer cells, MDA-MB-231, via formation of non-covalent complexes (PTX-LH2(M)) or covalent conjugates (PTX-LH2(C)). Moreover, LH2 showed prolonged circulation in the body and enhanced accumulation in tumors. Both PTX-LH2(M) and PTX-LH2(C) showed strong antitumor effects in a triple-negative breast cancer grafted mouse model at an extremely low dosage.

Automated summary

The designed pH-activatable cell-penetrating peptide dimer LH2 with histidine residues is able to penetrate cells specifically in weak acidic conditions, delivering paclitaxel effectively into triple-negative breast cancer cells. Both non-covalent complexes (PTX-LH2(M)) and covalent conjugates (PTX-LH2(C)) of LH2 show strong antitumor effects in a triple-negative breast cancer grafted mouse model at extremely low dosages, indicating potential for targeted drug delivery and therapy.