Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

中文翻译：

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X 射线荧光成像实现迭代纳米颗粒生物工程

纳米颗粒（NP）目前被开发用于药物输送和分子成像。然而，它们经常在到达目标之前被拦截，导致目标效率和信噪比较低。它们往往积聚在肺、肝、肾和脾等器官中。补救措施是迭代设计 NP 表面特性和管理策略，目前这是一个耗时的过程，包括在不同时间点进行器官解剖。为了改善这一点，我们提出了一种使用整体动物 X 射线荧光 (XRF) 成像的快速迭代方法来系统地评估 NP 体内分布。我们将此方法应用于基于钼的纳米粒子和氯膦酸盐脂质体，用于肿瘤靶向和瞬时巨噬细胞耗竭，从而减少肺和肝脏中的积累并最终检测到肿瘤。 XRF 计算机断层扫描 (XFCT) 提供了对肿瘤内 NP 分布的 3D 洞察。我们使用染料掺杂纳米颗粒的多尺度成像方法和用于纳米毒理学分析的基因表达分析来验证结果。 XRF 成像具有推进临床前药代动力学研究中的治疗和诊断的潜力。