Luo Siyuan, Zhao Chenyu, Wang Rong, Chang Zepu, Di Jingran, Wang Ya, Gan Zhenhai, Wu Daocheng
Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.
Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P. R. China.
Small. 2025 Feb;21(6):e2411188. doi: 10.1002/smll.202411188. Epub 2024 Dec 26.
To enhance tumor comprehensive therapeutic effect of nanomedicines, an efficient strategy that integrates polydopamine and IR780 photothermal therapy, glucose oxidase (GOx) starvation therapy, Banoxantrone (AQ4N) and Tirapazamine (TPZ) dual hypoxia chemotherapy is developed in chronological order. Higher tumor accumulation of porous dual infinite coordination polymer nanocomposites are designed and prepared to implement this strategy, in which fluorescent dye IR780 doped hypoxic prodrugs AQ4N and TPZ coordinated with Cu(II) as the core, this core is encapsulated by GOx-loaded porous polydopamine coordinated with Fe(III) (Fe-MPDA). These nanocomposites exhibit a particle dimension of 118.5 ± 21.7 nm with pore size of 20.1 nm (pore volume 0.012 cm g nm), facilitating easy accumulation in tumor tissues. Particularly, their ratio of the area under the curve (AUC) of the tumor/organ drug concentration versus time (AUC/AUC) is 1.28. Upon reaching the tumor, the nanocomposites release GOx and Fe-MPDA in initial stage to execute photothermal and starvation therapy, simultaneously enhance the hypoxic level at the tumor site. Then AQ4N and TPZ undergo synergistic chemotherapy in the enhanced hypoxic environment. Animal experiments show a tumor inhibition rate of 100% and a tumor recurrence rate of 0% after 60 d, demonstrating their great potential application for tumor treatment.
为提高纳米药物的肿瘤综合治疗效果，按时间顺序开发了一种整合聚多巴胺和IR780光热疗法、葡萄糖氧化酶（GOx）饥饿疗法、巴诺蒽醌（AQ4N）和替拉扎明（TPZ）双重缺氧化疗的有效策略。设计并制备了具有更高肿瘤蓄积性的多孔双无限配位聚合物纳米复合材料来实施该策略，其中以掺杂荧光染料IR780的缺氧前药AQ4N和TPZ与Cu（II）配位为核心，该核心被负载GOx的与Fe（III）配位的多孔聚多巴胺（Fe-MPDA）包裹。这些纳米复合材料的粒径为118.5±21.7nm，孔径为20.1nm（孔体积0.012cm g nm），便于在肿瘤组织中蓄积。特别是，它们的肿瘤/器官药物浓度与时间曲线下面积之比（AUC/AUC）为1.28。纳米复合材料到达肿瘤部位后，在初始阶段释放GOx和Fe-MPDA以进行光热和饥饿疗法，同时提高肿瘤部位的缺氧水平。然后AQ4N和TPZ在增强的缺氧环境中进行协同化疗。动物实验显示60d后肿瘤抑制率为100%，肿瘤复发率为0%，证明了它们在肿瘤治疗中的巨大潜在应用价值。
