Department of Biomaterials, The Higher Educational Key Laboratory for Biomedical Engineering of Fujian Province, Research Center of Biomedical Engineering of Xiamen, College of Materials, Xiamen University, 422 Siming South Road, Xiamen 361005, P. R. China.
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, P. R. China.
ACS Biomater Sci Eng. 2022 May 9;8(5):1942-1955. doi: 10.1021/acsbiomaterials.2c00076. Epub 2022 Mar 31.
The integration of reactive oxygen species (ROS)-based chemodynamic therapy (CDT) and photodynamic therapy (PDT) has attracted enormous attention for synergistic antitumor therapies. However, the strategy is severely hampered by tumor hypoxia and overproduced antioxidant glutathione (GSH) in the tumor microenvironment. Inspired by the concept of metal coordination-based nanomedicines, we proposed an effective strategy for synergistic cancer treatment in response to the special tumor microenvironmental properties. Herein, we present novel metal-coordinated multifunctional nanoparticles (NPs) by the Cu-triggered assembly of photosensitizer indocyanine green (ICG) and hypoxia-activated anticancer prodrug tirapazamine (TPZ) (Cu-ICG/TPZ NPs). After accumulating within tumor sites the enhanced permeability and retention (EPR) effect, the Cu-ICG/TPZ NPs were capable of triggering a cascade of combinational therapeutic reactions, including hyperthermia, GSH elimination, and Cu-mediated OH generation and the subsequent hypoxia-triggered chemotherapeutic effect of TPZ, thus achieving synergistic tumor therapy. Both and evaluations suggested that the multifunctional Cu-ICG/TPZ NPs could realize satisfactory therapeutic efficacy with excellent biosafety. These results thus suggested the great potential of Cu-ICG/TPZ NPs to serve as a metallodrug nanoagent for synergetically enhanced tumor treatment.
基于活性氧（ROS）的化学动力学疗法（CDT）与光动力疗法（PDT）的整合引起了人们对协同抗肿瘤疗法的极大关注。然而，该策略受到肿瘤缺氧和肿瘤微环境中过度产生的抗氧化谷胱甘肽（GSH）的严重阻碍。受基于金属配位的纳米药物概念的启发，我们针对特殊的肿瘤微环境特性提出了一种协同癌症治疗的有效策略。在此，我们通过光敏剂吲哚菁绿（ICG）和乏氧激活型抗癌前药替拉扎明（TPZ）的 Cu 触发组装，提出了一种新型的金属配位多功能纳米颗粒（NPs）（Cu-ICG/TPZ NPs）。在积累于肿瘤部位后，增强的通透性和保留（EPR）效应，Cu-ICG/TPZ NPs 能够触发一系列组合治疗反应，包括热疗、GSH 消除以及 Cu 介导的 OH 生成和随后的 TPZ 乏氧触发的化疗作用，从而实现协同肿瘤治疗。和体内评估均表明，多功能 Cu-ICG/TPZ NPs 能够实现令人满意的治疗效果，并具有优异的生物安全性。这些结果表明，Cu-ICG/TPZ NPs 作为一种金属药物纳米制剂，具有协同增强肿瘤治疗的巨大潜力。
