Cell-Penetrating Doxorubicin Released from Elastin-Like Polypeptide Kills Doxorubicin-Resistant Cancer Cells in In Vitro Study

Elastin-like polypeptides (ELPs) undergo a characteristic phase transition in response to ambient temperature. Therefore, it has been be used as thermosensitive vector for the delivery of chemotherapy agents since can target hyperthermic tumors. This novel strategy introduces unprecedented options treating cancer with fewer concerns about side effects. In this study, ELP system was further modified an enzyme-cleavable linker order release drugs within consists ELP, matrix metalloproteinase (MMP) substrate, cell-penetrating peptide (CPP), and 6-maleimidocaproyl amide derivative doxorubicin (Dox). shows up 4-fold increase cell penetration results more death breast cells compared ELP-Dox. Even doxorubicin-resistant (NCI/ADR MES-SA/Dx5), ELP-released demonstrated better membrane penetration, leading at least twice killing resistant ELP-Dox free Dox. MMP-digested CPP-Dox showed induced vitro. CPP-complexed Dox released from killed even Dox-resistant efficiently than both non-cleaved ELP-CPP-Dox.