Zhang Zhiqi, Tian Fangzheng, Lai Shiwei, Xu Xiaoxuan, Zhou Mei, Hou Zhenyu, Li Siyu, Zhang Jianqiong, Yang Xue, Xie Jinbing, Ju Shenghong
Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, 210009, China.
J Mater Chem B. 2025 Jul 2;13(26):7753-7768. doi: 10.1039/d5tb00071h.
Combined photothermal and photodynamic therapy is a promising strategy for the treatment of triple-negative breast cancer (TNBC) as it can accurately target tumor tissues and improve therapeutic efficacy. However, its efficacy is still insufficient owing to the heat resistance resulting from the upregulation of heat shock protein 90 (HSP90) and diminished reactive oxygen species (ROS) levels due to the accumulation of its client protein hypoxia-inducible factor-1α (HIF1α). Herein, SNX2112 (HSP90 inhibitor) and IR825 (photosensitizer) are loaded into a pH-responsive nano-micelle for efficient photothermal and photodynamic therapy. SNX2112 inhibits HSP90 activity to reduce heat resistance for enhanced photothermal therapy. Furthermore, HIF1α accumulation is reduced to increase ROS production to amplify photodynamic therapy efficacy. Consequently, the combined therapy enhanced by inhibiting HSP90-HIF1α effectively suppresses tumor growth synergistic effects, with high photothermal conversion and ROS productivity under mild temperature (42 °C). Furthermore, using SNX2112 improves the efficacy of the combined photothermal and photodynamic therapy, showing its eminent potential in TNBC treatment.
光热和光动力联合疗法是一种很有前景的三阴性乳腺癌（TNBC）治疗策略，因为它可以精确靶向肿瘤组织并提高治疗效果。然而，由于热休克蛋白90（HSP90）上调导致的耐热性以及其客户蛋白缺氧诱导因子-1α（HIF1α）积累导致的活性氧（ROS）水平降低，其疗效仍然不足。在此，将SNX2112（HSP90抑制剂）和IR825（光敏剂）负载到pH响应性纳米胶束中，用于高效的光热和光动力治疗。SNX2112抑制HSP90活性以降低耐热性，从而增强光热治疗。此外，减少HIF1α积累以增加ROS产生，从而放大光动力治疗效果。因此，通过抑制HSP90-HIF1α增强的联合疗法在温和温度（42°C）下具有高光热转换和ROS产生能力，有效抑制肿瘤生长并产生协同效应。此外，使用SNX2112提高了光热和光动力联合治疗的疗效，显示出其在TNBC治疗中的显著潜力。
