Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
Molecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
ACS Nano. 2024 Jul 2;18(26):16808-16818. doi: 10.1021/acsnano.4c02344. Epub 2024 Jun 13.
Amidst the rapid growth of protein therapeutics as a drug class, there is an increased focus on designing systems to effectively deliver proteins to target organs. Quantitative monitoring of protein distributions in tissues is essential for optimal development of delivery systems; however, existing strategies can have limited accuracy, making it difficult to assess suborgan dosing. Here, we describe a quantitative imaging approach that utilizes metal-coded mass tags and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify the suborgan distributions of proteins in tissues that have been delivered by polymeric nanocarriers. Using this approach, we measure nanomole per gram levels of proteins as delivered by guanidinium-functionalized poly(oxanorborneneimide) (PONI) polymers to various tissues, including the alveolar region of the lung. Due to the multiplexing capability of the LA-ICP-MS imaging, we are also able to simultaneously quantify protein and polymer distributions, obtaining valuable information about the relative excretion pathways of the protein cargo and carrier. This imaging approach will facilitate quantitative correlations between nanocarrier properties and protein cargo biodistributions.
在蛋白质治疗作为一种药物类别快速发展的背景下，人们越来越关注设计系统以将蛋白质有效递送到靶器官。定量监测组织中蛋白质的分布对于优化递药系统的开发至关重要；然而，现有的策略可能准确性有限，难以评估亚器官的剂量。在这里，我们描述了一种定量成像方法，该方法利用金属编码质量标签和激光烧蚀电感耦合等离子体质谱（LA-ICP-MS）来定量测量通过聚合物纳米载体递送到组织中的蛋白质的亚器官分布。使用这种方法，我们测量了胍基功能化聚（氧杂降冰片烯亚胺）（PONI）聚合物递送到各种组织（包括肺的肺泡区域）的蛋白质的纳摩尔/克水平。由于 LA-ICP-MS 成像的多重检测能力，我们还能够同时定量蛋白质和聚合物的分布，从而获得有关蛋白质货物和载体的相对排泄途径的有价值信息。这种成像方法将促进纳米载体特性与蛋白质货物生物分布之间的定量相关性。
