Cryoablation-activated enhanced nanodoxorubicin release for the therapy of chemoresistant mammary cancer stem-like cells.

Chemoresistance is a common property of tumor-initiating cancer stem-like cells. Overcoming chemoresistance, particularly in cancer stem-like cells, can markedly enhance the efficacy of cancer therapy and prevent cancer recurrence and metastasis. This study demonstrates that temperature-negative expansion nanodrugs could achieve the controllable and enhanced release of anticancer drugs when combined with cryoablation and effectively overcome chemoresistance in mammary cancer stem-like cells. The enhanced destruction of both cancer stem-like cells and cancer cells resulted in the improved inhibition of second-generation tumor formation in vitro. Furthermore, nanodrug-mediated cryosurgery did not produce systemic toxicity and had superior antitumor effects in a xenograft tumor model. Collectively, this study demonstrates the strong potential of thermally sensitive nanodrug-mediated cryoablation for overcoming chemoresistance in cancer stem-like cells and markedly improving the overall treatment efficacy against breast cancer.