X射线激发光动力疗法（X-PDT）采用X射线作为能量来源，克服了传统光动力疗法（PDT）的光穿透限制，但受到高能辐射和缺氧肿瘤微环境的限制。低剂量 X 射线激发光动力疗法和减少线粒体耗氧量可以成为克服这些障碍的重大突破。本研究制备了吸附光敏剂MC540并负载α-(硝酸酯)酸(NEAA)的NaLuF4:Tb/Gd (15%/5%)@NaYF4 (ScNP)纳米粒子作为低X射线剂量触发纳米粒子。闪烁体。获得的最终产物是NaLuF4:Tb/Gd (15%/5%)@NaYF4@mSiO2@MC540@NEAA (ScNP-MS@MC540@NEAA)纳米复合材料，表现出强烈的绿色发光。 X-PDT 产生细胞毒性活性氧 (ROS)，电离辐射损伤最小。同时，NEAA与谷胱甘肽（GSH）反应生成一氧化氮（NO），对受损的线粒体呼吸链进行气态处理，减少耗氧量，缓解缺氧，增强X-PDT疗效，实现闭环治疗。超氧离子（˙O2-）可以与产生的NO快速反应，形成高细胞毒性的活性氮（RNS）过氧亚硝酸根阴离子（ONOO-），与ROS相比，其具有更高的细胞毒性。此外，GSH还能清除有毒的ROS并维持肿瘤细胞的生理功能。它可以诱导癌细胞过度氧化和亚硝化应激。该工作描述了一种总辐射为50 mGy的低剂量X射线触发X-PDT系统，涉及GSH消耗、自供NO、减轻线粒体损伤、缓解缺氧以产生ROS和RNS，形成封闭的环路抗缺氧双模式系统，协同增强抗肿瘤作用，且无明显生物副作用。为深部肿瘤X-PDT提供了良好的平台，具有广阔的应用前景。

X-ray-excited photodynamic therapy (X-PDT) employs X-rays as an energy source, overcoming the light penetration limitations of traditional photodynamic therapy (PDT) but is constrained by high-energy radiation and the hypoxic tumor microenvironment. Low-dose X-ray-excited photodynamic therapy and reduction of mitochondrial oxygen consumption can serve as significant breakthroughs in overcoming these barriers. In this study, NaLuF4:Tb/Gd (15%/5%)@NaYF4 (ScNP) nanoparticles adsorbing the photosensitizer MC540 and loaded with α-(nitrate ester) acid (NEAA) were prepared as low X-ray dose triggered nano-scintillators. The final product obtained was NaLuF4:Tb/Gd (15%/5%)@NaYF4@mSiO2@MC540@NEAA (ScNP-MS@MC540@NEAA) nanocomposites, which exhibited intense green luminescence. X-PDT generates cytotoxic reactive oxygen species (ROS) with minimal ionizing radiation damage. Simultaneously, NEAA reacts with glutathione (GSH) to generate nitric oxide (NO) for gaseous treatment of the damaged mitochondrial respiratory chain to reduce oxygen consumption and alleviate hypoxia, enhancing the X-PDT efficacy and realizing a closed-loop treatment. The superoxide ions (˙O2-) can rapidly react with NO produced to form the highly cytotoxic reactive nitrogen species (RNS) peroxynitrite anion (ONOO-), which exhibits higher cytotoxicity compared to ROS. Furthermore, GSH scavenges toxic ROS and maintains the physiological function of tumor cells. It can induce cancer cell overoxidation and nitrosative stress. This work describes a low-dose X-ray-triggered X-PDT system with total radiation of 50 mGy, which involves GSH consumption, self-supplied NO, mitochondrial damage alleviation, and hypoxia relief to generate ROS and RNS, forming a closed-loop anti-hypoxia dual-mode system with synergistically enhanced anti-tumor effects, without significant biological side effects. It provides a promising platform for deep-seated tumor X-PDT with considerable application prospects.