School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
College of Environmental Science and Engineering/Sino-Canada Joint R&D Centre for Water and Environmental Safety, Nankai University, Tianjin 300071, P. R. China.
J Mater Chem B. 2024 Apr 3;12(14):3509-3520. doi: 10.1039/d3tb02576d.
Both chemodynamic therapy and photodynamic therapy, based on the production of reactive oxygen (ROS), have excellent potential in cancer therapy. However, the abnormal redox homeostasis in tumor cells, especially the overexpressed glutathione (GSH) could scavenge ROS and reduce the anti-tumor efficiency. Therefore, it is essential to develop a simple and effective tumor-specific drug delivery system for modulating the tumor microenvironment (TME) and achieving synergistic therapy at the tumor site. In this study, self-assembled nanoparticles (named CDZP NPs) were developed using copper ion (Cu), doxorubicin (Dox), zinc phthalocyanine (ZnPc) and a trace amount of poly(2-(di-methylamino)ethylmethacrylate)-poly[()-3-hydroxybutyrate]-poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA-PHB-PDMAEMA) through chelation, π-π stacking and hydrophobic interaction. These triple factor-responsive (pH, laser and GSH) nanoparticles demonstrated unique advantages through the synergistic effect. Highly controllable drug release ensured its effectiveness at the tumor site, Dox-induced chemotherapy and ZnPc-mediated fluorescence (FL) imaging exhibited the distribution of nanoparticles. Meanwhile, Cu-mediated GSH-consumption not only reduced the intracellular ROS elimination but also produced Cu to catalyze hydrogen peroxide (HO) and generated hydroxyl radicals (˙OH), thereby enhancing the chemodynamic and photodynamic therapy. Herein, this study provides a green and relatively simple method for preparing multifunctional nanoparticles that can effectively modulate the TME and improve synergetic cancer therapy.
化学动力学治疗和光动力治疗都基于活性氧（ROS）的产生，在癌症治疗方面具有巨大的潜力。然而，肿瘤细胞中异常的氧化还原稳态，特别是过度表达的谷胱甘肽（GSH），可以清除 ROS 并降低抗肿瘤效率。因此，开发一种简单有效的肿瘤特异性药物递送系统来调节肿瘤微环境（TME）并在肿瘤部位实现协同治疗至关重要。在这项研究中，通过螯合、π-π 堆积和疏水相互作用，使用铜离子（Cu）、阿霉素（Dox）、锌酞菁（ZnPc）和微量聚[（2-（二甲氨基）乙基）甲基丙烯酸酯]-聚[（）-3-羟基丁酸]-聚[（2-（二甲氨基）乙基）甲基丙烯酸酯]（PDMAEMA-PHB-PDMAEMA）自组装成纳米粒子（命名为 CDZP NPs）。这些三重因素响应（pH、激光和 GSH）纳米粒子通过协同作用具有独特的优势。高度可控的药物释放确保了其在肿瘤部位的有效性，阿霉素诱导的化疗和 ZnPc 介导的荧光（FL）成像显示了纳米粒子的分布。同时，Cu 介导的 GSH 消耗不仅减少了细胞内 ROS 的消除，而且还产生了 Cu 来催化过氧化氢（HO）并产生羟基自由基（˙OH），从而增强了化学动力学和光动力治疗。本研究提供了一种绿色且相对简单的方法来制备多功能纳米粒子，可有效调节肿瘤微环境并提高协同癌症治疗效果。
