Evaluation of epirubicin-loaded trastuzumabe-modified immunoliposomes and imunomagnetoliposomes in the breast cancer therapy

Abstract

Breast cancer accounts for approximately 11-12% of all diagnosed cancer worldwide, representing the main cause of death among women. Among them, about 20% of patients have overexpression of human epithelial receptor (HER2), which is associated with higher lethality and susceptibility to brain metastasis. Epirubicin (EPI) is a potent chemotherapeutic agent used in breast cancer treatment, however, the presence of multidrug resistance mechanisms and side effects have limited its therapeutic action. The loading of EPI in immunoliposomes functionalized with trastuzumab (antibody anti-HER2) is a strategy to improve the therapeutic efficacy through their active targeting for tumor cells. Furthermore, the association of immunoliposomes with magnetic nanoparticles (immunomagnetoliposomes) can also improve the delivery of EPI to tumoral tissue besides promoting cellular death by hyperthermia magnetic. In this context, the present study aims to develop, characterize and evaluate the in vitro and in vivo antitumoral activity of trastuzumab-modified and epirubicin-loaded immunoliposomes and immunomagnetoliposomes for breast cancer treatment. Physicochemical characterization of them will be performed through particle size, polydispersity index, zeta potential, encapsulation efficiency, trastuzumab integrity, functionalization efficiency, magnetization property, and electron microscopy. The in vitro antitumoral activity will be evaluated using bi-dimensional (2D) and three-dimensional (3D) cell cultures through cytotoxicity (resazurin) and uptake assays (confocal microscopy and flow cytometry). Furthermore, the in vivo efficacy will be performed using a xerographic model, with or without hyperthermia treatment.