In this study, DOX was loaded in β-cyclodextrin based nanosponges (BNS-DOX), and the effect of DOX and BNS-DOX was compared in vitro in human and mouse breast cancer cell lines, either sensitive or resistant to DOX, and in vivo in the growth of spontaneous mammary cancer in BALB-neuT mice, which mimics some of the most critical features of the human disease and represents a real model of human epidermal growth factor receptor 2 (HER2) positive breast cancer [13]. Here, ERBB2 is linked to breast cancer.