(1) Background: Though X-ray excited photodynamic therapy (X-PDT) breakthrough the bottom neck of PDT application in deep tumor by overcoming light penetration depth limitation, the quantum yield of the hydrophilic X-PDT nanoparticles (NPs) still hampered its further application in vivo. Thus, establishing a proper hydrophilic decoration method which can maximally maintain the quantum yield of X-ray excited luminescent NPs is of urgent demand. (2) Methods: We synthesized NaGdF4: [Formula: see text] (NGF) as X-ray excited luminescent NPs and conducted hydrophilic decoration by two hydrophilic ligands, polyethylene glycol-NH2 (PEG) and cysteamine (Cy) via place exchange reaction, and coupled with photosensitizer (MC540) to form a X-PDT nanosystem. We also conducted experiments in vitro and in vivo to evaluate the efficacy of the X-PDT system. (3) Results: Both PEG and Cy decoration NPs presented excellent emission intensity, which could well excite the coupled photosensitizer MC540 to generate significant X-PDT efficacy under low-dose X-ray radiation. Especially for the NGF-Cy-MC540 treatment group, the cell viability reduced to [Formula: see text]% under 0.3[Formula: see text]Gy radiation and [Formula: see text]% under only 0.1[Formula: see text]Gy radiation, which is the lowest radiation dosage in the literature reports so far. In vivo experiment showed about 36% of tumor inhibition rate under 0.3[Formula: see text]Gy X-ray. Besides, no biotoxicity was observed in NGF groups even in high concentrations, demonstrating good biocompatibility. (4) Conclusions: The hydrophilic decoration method by Cy or PEG via place exchange reaction may pave a brand new way and strategy for X-PDT further clinical application.

中文翻译：

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亲水修饰对X射线激发发光纳米粒子对单线态氧产生的影响

(1) 背景：虽然 X 射线激发光动力疗法 (X-PDT) 通过克服光穿透深度限制突破了 PDT 在深部肿瘤中的应用，但亲水性 X-PDT 纳米粒子 (NPs) 的量子产率仍然阻碍了其在深部肿瘤中的应用。体内进一步应用。因此，迫切需要建立一种合适的亲水性装饰方法，以最大限度地保持 X 射线激发的发光 NPs 的量子产率。(2) 方法：我们合成了 NaGdF4: [公式：见正文] (NGF) 作为 X 射线激发的发光 NP，并通过两个亲水配体聚乙二醇-NH 进行亲水修饰2(PEG)和半胱胺(Cy)通过位置交换反应，并与光敏剂(MC540)偶联形成X-PDT纳米系统。我们还在体外和体内进行了实验，以评估 X-PDT 系统的功效。(3)结果：PEG和Cy修饰NPs均表现出优异的发射强度，在低剂量X射线辐射下，可以很好地激发耦合光敏剂MC540产生显着的X-PDT功效。尤其是NGF-Cy-MC540治疗组，细胞活力在0.3[公式：见文]Gy辐射下降至[公式：见文]%，[公式：见文]%仅在0.1[公式：见文]下Gy辐射，这是迄今为止文献报道的最低辐射剂量。体内实验表明，在0.3[公式：见正文]Gy X射线下，肿瘤抑制率约为36%。除了，即使在高浓度下，NGF 组也没有观察到生物毒性，证明了良好的生物相容性。(4)结论：Cy或PEG通过位点交换反应的亲水修饰方法可能为X-PDT进一步临床应用开辟一条全新的途径和策略。