Targeting self-assembled F127-peptide polymer with pH sensitivity for release of anticancer drugs

The treatment of breast cancer mainly relies on chemotherapy drugs, which present significant side effects. The most typical example is the cardiotoxicity and bone marrow suppression associated with doxorubicin (DOX). Therefore, this drug is not the first choice in clinical treatment. We designed ATN-FFPFF-ATN, a new targeted antitumor drug carrier, polymerized from phenylalanine dipeptide (FF), ATN-161 peptide, and Pluronic® F-127. The peptide and Pluronic® F-127 are linked with acetal and are, therefore, acid-sensitive. As cancer can reduce pH through complex mechanisms and subsequently maintain acid ambience, our vehicle can smartly unravel at a peculiar position, through which the drug can specifically accumulate inside the tumor. ATN-161 is a protein ligand of integrin α(5)β(1), which is highly expressed on the surface of some breast cancer cells. This targeting peptide sequence can play a role in the selective delivery of DOX to tumor cells. The DOX-carrying vector was able to significantly inhibit cell proliferation and promote cell apoptosis in MDA-MB-231 cells. Based on these results, ATN-FFPFF-ATN with pH response is a promising vehicle for DOX delivery.