Antiangiogenesis Combined with Inhibition of the Hypoxia Pathway Facilitates Low-Dose, X-ray-Induced Photodynamic Therapy.
Antiangiogenesis Combined with Inhibition of the Hypoxia Pathway Facilitates Low-Dose, X-ray-Induced Photodynamic Therapy.
复制标题
抗血管生成与缺氧途径抑制相结合，有利于低剂量、X 射线诱导的光动力治疗。
DOI：
10.1021/acsnano.1c01063
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发表时间：
2021
期刊：
影响因子：
17.1
通讯作者：
Wanwan Li
中科院分区：
文献类型：
--
作者：
Zhao Jiang;Liangrui He;Xujiang Yu;Zhiwen Yang;Weijie Wu;Xiaoyan Wang;R. Mao;D. Cui;Xiaoyuan Chen;Wanwan Li
X射线诱导光动力疗法（XPDT）在治疗深部肿瘤方面具有压倒性的上级优势。然而，由于纳米闪烁体的闪烁性能差、治疗性纳米平台的能量传递效率低以及肿瘤组织中存在的缺氧环境的组合，仍然存在限制。总的来说，这些降低了XPDT的疗效。在这里，我们报告了一种高效，低剂量的XPDT实现系统优化，从闪烁效率，纳米平台结构，治疗方法。我们开发了一种生物相容性，共掺杂的CaF2纳米闪烁体，其发出足够的绿色放射性发光，其亮度足以被肉眼看到。使用树枝状聚合物作为框架，我们建立了一个具有双核卫星架构的纳米平台，该架构能够在程序上和空间上分离治疗剂的双负载。这种策略允许组合XPDT和抗血管生成疗法的制造，从而产生能够同时攻击肿瘤的治疗系统。暴露于超低剂量辐射后，XPDT导致显著的肿瘤缩小，而抗血管生成药物有效地阻断了XPDT介导的缺氧所加剧的肿瘤血管形成，呈现出明显的协同效应。该系统还显示出较高的生物安全性，因为所采用的药剂已用于临床，并且Ca和F元素在人体中广泛存在。综合以上研究结果，为构建结构复杂、功能多样化的复合多承载建筑提供了参考。这项工作提供了一个更安全和更强大的应用组合XPDT和抗血管生成在未来的临床治疗设置。
X-ray-induced photodynamic therapy (XPDT) is overwhelmingly superior in treating deep-seated cancers. However, limitations remain, owing to a combination of the poor scintillation performance of the nanoscintillator, low energy transfer efficiency of the therapeutic nanoplatform, and hypoxic environment presented in the tumor tissue. Collectively, these reduce the curative effect of XPDT. Here, we report a highly efficient, low-dose XPDT realized by systematic optimization from scintillation efficiency, nanoplatform structure, to therapeutic approach. We developed a biocompatible, codoped CaF2 nanoscintillator that emitted sufficiently green radioluminescence that was bright enough to be seen by the naked eye. Using dendrimers as a framework, we built a nanoplatform featuring a dual-core-satellite architecture, which enabled both procedurally and spatially separate dual-loading of therapeutic agents. This strategy allowed for the fabrication of a combined XPDT and antiangiogenic therapy, resulting in a therapeutic system capable of simultaneous tumor attacks. After exposure to ultralow dose radiation, XPDT resulted in marked tumor reduction while the antiangiogenic drug effectively blocked tumor vascularization exacerbated by XPDT-mediated hypoxia, rendering a pronounced synergy effect. This system also showed high biosafety, as the agents adopted had been used clinically and both Ca and F elements were widespread in the human body. Taken together, the findings presented here provided a reference for the construction of complex, multiloading architecture in coordination with structural complexity and functional diversification. This work provided a safer and more robust application of the combined XPDT and antiangiogenesis in future clinical treatment settings.