DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression

• DOI: 10.1002/advs.202206707
• Publication Date: 2023-04-17T08:54:16Z
• Authors: Zuqin Chen; Sunfan Li; Fangzhou Li; Cheng Qin; Xianlei Li; Guangchao Qing; Jinjin Wang; Bozhang Xia; Fuxue Zhang; Liangliang Meng; Xing‐Jie Liang; Yueyong Xiao
• Keywords: Science; Q; heat shock protein; polymeric micelle; Triple Negative Breast Neoplasms; Phototherapy; chemotherapy; mitoxantrone; 3. Good health; DNA damage; mild‐photothermal therapy; Humans; HSP70 Heat-Shock Proteins; Mitoxantrone; Research Articles; Micelles

AbstractPatients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO‐micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild‐photothermal chemotherapy strategy based on MTO‐micelles has a promising prospect in the clinical transformation of TNBC treatment.