Zhao Yuanru, Zhang Yujie, Zhang Yan, Zhang Yuanyuan, Deng Zhichao, Bai Ting, Zhang Mingxin, Zhang Mingzhen, Song Jian
Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, China.
School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Small Methods. 2025 Jul;9(7):e2402091. doi: 10.1002/smtd.202402091. Epub 2025 Jan 26.
The application of a multimodal combination therapy based on a targeted nanodelivery system has been demonstrated to be more valuable in the treatment of cancer. In this work, a hollow polydopamine delivery system (CCC@HP@M) was designed to achieve sonodynamic and calcium-overload combined therapy for colon cancer. The CCC@HP@M exhibits both homologous tumour-targeting ability and pH-responsive drug release properties, enabling the simultaneous targeted delivery of CaO nanoparticles/sonosensitizer Ce6/autophagy inhibitor CQ. The CaO nanoparticles as calcium agents capable of triggering Ca overload in tumor cells. The oxidative stress produced by sonodynamic therapy is facilitated by the disruption of calcium homeostasis to enhance the effect of Ca overload-induced apoptosis. Furthermore, the O produced by CaO augments the sensitization of sonodynamic therapy. The autophagy inhibitor CQ can inhibit protective cellular autophagy, which is activated by sonodynamic therapy and Ca overload. Consequently, autophagy blockage can ensure the therapeutic effect of sonodynamic and Ca-overload combined therapy for colon cancer. The results of experiments in vitro and in vivo demonstrate that the stimulus-responsive targeted delivery system achieves autophagy blockage augmented sonodynamic and Ca-overload combined therapy of colon cancer. This work offers a promising theoretical basis for optimizing combined treatment strategies for tumors and clinical translational applications.
基于靶向纳米递送系统的多模态联合疗法在癌症治疗中已被证明更具价值。在这项工作中，设计了一种中空聚多巴胺递送系统（CCC@HP@M），以实现结肠癌的声动力和钙超载联合治疗。CCC@HP@M具有同源肿瘤靶向能力和pH响应药物释放特性，能够同时靶向递送CaO纳米颗粒/声敏剂Ce6/自噬抑制剂CQ。CaO纳米颗粒作为钙剂，能够触发肿瘤细胞中的钙超载。声动力疗法产生的氧化应激通过破坏钙稳态来促进，以增强钙超载诱导的细胞凋亡效果。此外，CaO产生的O增强了声动力疗法的敏感性。自噬抑制剂CQ可以抑制保护性细胞自噬，而这种自噬是由声动力疗法和钙超载激活的。因此，自噬阻断可以确保声动力和钙超载联合治疗结肠癌的疗效。体外和体内实验结果表明，这种刺激响应性靶向递送系统实现了自噬阻断增强的结肠癌声动力和钙超载联合治疗。这项工作为优化肿瘤联合治疗策略和临床转化应用提供了有前景的理论基础。
