1 IMPROVING QUANTITATIVE BIODISTRIBUTION ANALYSIS

Quantitative biodistribution measurements can provide essential information related to the potential toxicity and efficacy of drugs and drug delivery systems. Because of this, accurate biodistribution data can be used to inform the design and implementation of delivery systems that necessitate high levels of targeting, or low levels of off‐site accumulation. While there exist highly sensitive approaches to measure biodistribution (e.g., radiotracing), biodegradable delivery systems present a unique challenge as radiolabels can be unpredictably released during delivery system storage or biodegradation, which can lead to inaccurate biodistribution measurements. In this issue of Bioengineering & Translational Medicine, a team led by Professor Silvia Muro from the Institute for Bioscience and Biotechnology Research at the University of Maryland, College Park, and the Institute for Bioengineering of Catalonia of the Barcelona Institute of Science and Technology, describes an approach to separate unbound radiolabels from polymer‐bound radiolabels so as to accurately quantify the biodistribution of a DNA‐based delivery system termed 3DNA. It was demonstrated that ¹²⁵I radiolabels were released from ¹²⁵I‐labeled‐3DNA carriers upon introduction into biological fluids or tissues, thus demonstrating the need to separate the signals from the released radiolabel and the still‐carrier‐bound radiolabel. The authors then show that through precipitation initiated with trichloroacetic acid, free radiolabel could be quantified separately from the radiolabeled carrier. Importantly, biodistribution of ¹²⁵I‐labeled‐3DNA could not be accurately quantified by simply considering the biodistribution of a separate control with free ¹²⁵I radiolabel; instead, to accurately (>85% accuracy) quantify biodistribution of ¹²⁵I‐labeled‐3DNA, the free ¹²⁵I radiolabel must be precipitated out of each organ for each individual experiment. Overall, this study describes an important step in accurately quantifying the biodistribution of radiolabeled, biodegradable, delivery systems.

DOI: 10.1002/btm2.10208

中文翻译：

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BioTM Buzz（第6卷，第2期）

1改进定量生物分布分析

定量生物分布测量可以提供与药物和药物输送系统的潜在毒性和功效有关的基本信息。因此，准确的生物分布数据可用于指导需要高水平靶向或低水平异地积累的输送系统的设计和实施。尽管存在高度敏感的方法来测量生物分布（例如，放射性示踪），但是可生物降解的递送系统提出了独特的挑战，因为在递送系统的储存或生物降解过程中，放射性标记可能会不可预测地释放，这可能导致生物分布测量不准确。在本期《生物工程与转化医学》中马里兰大学学院生物科学与生物技术研究所的Silvia Muro教授和巴塞罗那科学技术大学加泰罗尼亚生物工程研究所的一个团队描述了一种从聚合物中分离未结合的放射性标记的方法结合放射性标记，以准确量化称为3DNA的基于DNA的递送系统的生物分布。事实证明，¹²⁵ I的放射性标记是从¹²⁵释放的I-标记的3DNA载体一经引入生物体液或组织中，就表明需要将信号与释放的放射性标记和仍然与载体结合的放射性标记分开。作者然后表明，通过用三氯乙酸引发的沉淀，可以将游离的放射性标记物与放射性标记的载体分开进行定量。重要的是，仅考虑具有游离¹²⁵ I放射性标记的单独对照的生物分布，就无法准确定量¹²⁵ I标记的3DNA的生物分布。相反，要准确地（> 85％的准确度）定量¹²⁵ I标记的3DNA的生物分布，免费的¹²⁵对于每个单独的实验，必须从每个器官中沉淀出放射性标记。总的来说，这项研究描述了准确量化放射性标记的，可生物降解的递送系统的生物分布的重要步骤。

DOI：10.1002 / btm2.10208