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DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression
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DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression
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Journal Article
DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild‐Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression
2023
Overview
Patients 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. A multifunctional drug delivery system (MTO‐micelles) based on the chemotherapeutic drug mitoxantrone (MTO) and amphiphilic polymer DSPE‐PEG2000 is developed. MTO induced DNA damage amplify the effect of Mild‐photothermal Chemotherapy by downregulating HSP70 expression. This mild‐photothermal chemotherapeutic formulation provides a facile and effective way for the TNBC treatment.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
