美国麻省理工学院Richard A. Young研究小组发现，肿瘤药物会在细胞核缩合物中聚集。相关论文于2020年6月19日发表于国际学术期刊《科学》。

研究人员检测了细胞核缩合物是否浓缩了小分子癌症治疗药物，从而改变了它们的药效特性。研究人员发现抗肿瘤药在体外能够集中在特定的蛋白质缩合物中，并且这是通过与药物靶标无关的物理化学性质发生的。在肿瘤细胞中也观察到这种行为，即药物隔离会影响药物活性。

研究人员发现，改变缩合物的性质会影响药物的浓度和活性。这些结果表明，缩合物中小分子的选择性分配和浓缩有助于药物动力学，并且对该现象的进一步理解可能有助于疾病疗法的发展。

据悉，细胞包含各种相分离的缩合物，从而将具有独特理化性质的生物分子分隔并浓缩。

附：英文原文

Title: Partitioning of cancer therapeutics in nuclear condensates

Author: Isaac A. Klein, Ann Boija, Lena K. Afeyan, Susana Wilson Hawken, Mengyang Fan, Alessandra DallAgnese, Ozgur Oksuz, Jonathan E. Henninger, Krishna Shrinivas, Benjamin R. Sabari, Ido Sagi, Victoria E. Clark, Jesse M. Platt, Mrityunjoy Kar, Patrick M. McCall, Alicia V. Zamudio, John C. Manteiga, Eliot L. Coffey, Charles H. Li, Nancy M. Hannett, Yang Eric Guo, Tim-Michael Decker, Tong Ihn Lee, Tinghu Zhang, Jing-Ke Weng, Dylan J. Taatjes, Arup Chakraborty, Phillip A. Sharp, Young Tae Chang, Anthony A. Hyman, Nathanael S. Gray, Richard A. Young

Issue&Volume: 2020/06/19

Abstract: The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.

DOI: 10.1126/science.aaz4427

Source: https://science.sciencemag.org/content/368/6497/1386