Reactive Oxygen Species‐Triggered Hydrogen Sulfide Release and Cancer‐Selective Antiproliferative Effect of Anethole Dithiolethione‐Containing Polymeric Micelles
Reactive Oxygen Species‐Triggered Hydrogen Sulfide Release and Cancer‐Selective Antiproliferative Effect of Anethole Dithiolethione‐Containing Polymeric Micelles
复制标题
活性氧——触发硫化氢释放和癌症——茴香脑二硫硫酮的选择性抗增殖作用——含有聚合物胶束
DOI：
10.1002/adhm.202201836
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发表时间：
2023
影响因子：
10
通讯作者：
Hasegawa, Urara
中科院分区：
文献类型：
--
作者：
van der Vlies, André J.;Ghasemi, Masoud;Adair, Bernadette M.;Adair, James H.;Gomez, Enrique D.;Hasegawa, Urara
硫化氢（H2S）是人体内的气体信号分子，并且由于其在癌细胞增殖和迁移中的调节作用而在癌症治疗中引起关注。越来越多的证据表明，持续向癌细胞输送H2S长时间可抑制癌症进展。然而，H2S的治疗应用中的一个主要挑战是其受控递送。为了解决这个问题，开发了含有H2S供体-茴香脑二硫杂环戊烯硫酮（ADT）基团的聚合物胶束，其H2S释放曲线对于抑制癌细胞增殖是最佳的。胶束在被细胞内存在的活性氧物质（ROS）氧化后释放H2S。H2S释放曲线可以通过改变聚合物设计来控制。此外，在体外试验中，显示中等H2S释放速率的胶束在人结肠癌细胞以及鸡绒毛尿囊膜癌模型中发挥最强的抗增殖作用，而胶束不影响人脐静脉内皮细胞的增殖。这项研究显示了使用胶束方法微调H2S释放曲线以实现H2S在癌症治疗中的全部治疗潜力的重要性。
Hydrogen sulfide (H2S) is a gaseous signaling molecule in the human body and has attracted attention in cancer therapy due to its regulatory roles in cancer cell proliferation and migration. Accumulating evidence suggests that continuous delivery of H2S to cancer cells for extended periods of time suppresses cancer progression. However, one major challenge in therapeutic applications of H2S is its controlled delivery. To solve this problem, polymeric micelles are developed containing H2S donating‐anethole dithiolethione (ADT) groups, with H2S release profiles optimal for suppressing cancer cell proliferation. The micelles release H2S upon oxidation by reactive oxygens species (ROS) that are present inside the cells. The H2S release profiles can be controlled by changing the polymer design. Furthermore, the micelles that show a moderate H2S release rate exert the strongest anti‐proliferative effect in human colon cancer cells in in vitro assays as well as the chick chorioallantoic membrane cancer model, while the micelles do not affect proliferation of human umbilical vein endothelial cells. This study shows the importance of fine‐tuning H2S release profiles using a micelle approach for realizing the full therapeutic potential of H2S in cancer treatment.