Anticancer effect of metformin in herceptin‐conjugated liposome for breast cancer

Abstract

Metformin (MET) is an anti‐diabetic drug effective against breast cancer, targeting breast cancer stem cells (BCSCs). MET‐encapsulating liposome (LP‐MET) and Herceptin‐conjugated LP‐ MET (Her‐LP‐MET) were evaluated for their anti‐cancer effect in vitro and in vivo. Size and zeta potentials of LP‐MET and Her‐LP‐MET were suitable for enhanced permeability and retention effects. Her‐LP‐MET yielded greater inhibition of BCSC proliferation in vitro than free MET or LP‐ MET, as well as a dose‐dependent long‐term anti‐proliferation effect. Further, the anti‐migration effect of Her‐LP‐MET on BCSCs was superior to that of MET or LP‐MET, and was enhanced when used in concert with doxorubicin (DOX). In a mouse model, Her‐LP‐MET combined with free DOX was more effective than free MET, free DOX, or Her‐LP‐MET. Moreover, Her‐LP‐MET combined with free DOX yielded tumor remission, whereas free DOX alone resulted in metastasis or death. As such, Her‐LP‐MET formulation is expected to provide a new therapeutic modality targeting BCSCs.