METAL-ORGANIC FRAMEWORK AS PROTECTIVE COATING FOR CANCER BIOSPECIMEN PRESERVATION

总结 癌症研究和早期发现癌症的临床诊断依赖于高质量的 例如血液、尿液和唾液的生物流体。在这些生物流体中，分子生物标志物的完整性和 从其分析中获得的信息的质量高度依赖于预处理期间的储存条件。 分析阶段。不幸的是，由于生物分子（特别是蛋白质）在环境温度下的稳定性差， 在高温下，它们在分析之前容易失去其结构和生物功能性。因此，广泛的 制冷分配网络，“冷链”，是必要的，以保持最佳温度， 运输、储存和处理这些生物标本。除了造成巨大的财政和 环境负担，冷链系统在院前和资源有限的环境中根本不可行 例如城市和农村诊所，以及中低收入发展中国家， 制冷和电力没有保障。此外，当生物流体被冷冻时， 热力学自由能和不利的冰晶-蛋白质相互作用可能发生在随后的过程中， 解冻，这可能进一步损害分析物的完整性。上述考虑清楚地表明， 对于用于在预分析阶段期间保存生物流体中的分子生物标记的替代方法， 优选不需要冷藏。在这个探索性的项目中，我们提出了一种新的方法， 涉及使用金属-有机框架（MOF）作为用于保持 在正常（非冷藏）储存条件下生物流体中的生物标志物。这里建议的方法是 彻底消除了对冷藏的需求，避免了不必要的冻融 循环并克服了巨大的经济和环境负担。这种节能环保的- 友好的方法不仅代表了一种新的技术，以消除冷链和温度控制 处理癌症相关的生物标本，而且还允许按需中断、存储和重新启动 在稍后的时间以集中的方式/位置进行检测，以提高临床诊断的可靠性。 为了实现这一最终目标，我们将（i）开发和评估基于MOF的肾癌保存- 在波动的（未调节的）环境温度和湿度下患者尿液中的相关蛋白质生物标志物 （ii）开发和评估基于MOF的前列腺癌相关生物标志物的保存， 患者血清/血浆在波动的温度和湿度下。一旦这个早期，创新和探索 项目完成后，我们将奠定基础，并部分开发基于MOF的可中断， 用于临床中癌症相关分子生物标志物可储存和可重复的生物保存方法 生物标本，它克服了制冷要求，并使按需生物分析在一个 集中式/分布式方式。为下一步做好准备，开发一种轻便、多功能、 低成本的基于MOF的技术，用于保存不同的环境敏感的生物分子， 用于癌症研究和临床生物分析的细胞和大块组织。

Summary Cancer research and clinical diagnostics for early detection of cancer rely on the availability of high-quality biofluids such as blood, urine, and saliva. Within these biofluids, the integrity of molecular biomarkers and the quality of information obtained from their analysis is highly dependent on the storage conditions during pre- analytical phase. Unfortunately, due to the poor stability of biomolecules (especially proteins) at ambient temperatures, they are prone to lose their structure and biofunctionality before analysis. Hence, an extensive distribution network of refrigeration, the “cold chain”, is necessary to maintain an optimal temperature during transport, storage, and handling of these biospecimens. Apart from causing a huge financial and environmental burden, the cold chain system is simply not feasible in pre-hospital and resource-limited settings such as urban and rural clinics, as well as developing countries with low and moderate incomes, where refrigeration and electricity are not guaranteed. Moreover, when the biofluids are frozen, decrease in thermodynamic free energy and unfavorable ice crystal-protein interactions can occur during subsequent thawing, which can further compromise analyte integrity. The above considerations clearly suggest the need for an alternate approach for preserving molecular biomarkers in biofluids during the pre-analytical stage, preferably, without the need for refrigeration. In this exploratory project, we propose a novel approach that involves the use of metal-organic frameworks (MOFs) as encapsulants for preserving the integrity of biomarkers in biofluids under normal (non-refrigerated) storage conditions. The approach suggested here is transformative in that it completely eliminates the need for refrigeration and avoids unwanted freeze-thaw cycles and overcomes a huge economic and environmental burden. This energy-efficient and environmentally- friendly approach not only represents a novel technique to eliminate the cold chain and temperature-controlled handling of cancer-related biospecimens, but also allows interruptible, storable, and restorable on-demand detection at a later time in a centralized manner/location to improve the reliability of clinical diagnostics. Towards this ultimate goal, we will (i) Develop and assess the MOF-based preservation of kidney cancer- related protein biomarkers in patient urine under fluctuating (unregulated) ambient temperature and humidity conditions; and (ii) Develop and assess the MOF-based preservation of prostate cancer-related biomarkers in patient serum/plasma under fluctuating temperature and humidity. Once this early, innovative and exploratory project is completed, we will have laid the groundwork and partially developed MOF-based interruptible, storable, and restorable biopreservation approach for cancer-related molecular biomarkers in clinical biospecimens, which overcomes the refrigeration requirement and enables on-demand bioanalytics in a centralized/distributed manner. The stage would be set for the next step, developing a facile, versatile and low-cost MOF-based technique for the preservation of different environmentally sensitive biomolecules, whole cells and bulk tissues for cancer research and clinical bioanalytics.