TY - JOUR
T1 - Reactive Oxygen Species-Triggered Hydrogen Sulfide Release and Cancer-Selective Antiproliferative Effect of Anethole Dithiolethione-Containing Polymeric Micelles
AU - van der Vlies, André J.
AU - Ghasemi, Masoud
AU - Adair, Bernadette M.
AU - Adair, James H.
AU - Gomez, Enrique D.
AU - Hasegawa, Urara
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
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U2 - 10.1002/adhm.202201836
DO - 10.1002/adhm.202201836
M3 - Article
C2 - 36495554
AN - SCOPUS:85147266346
SN - 2192-2640
VL - 12
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 6
M1 - 2201836
ER -
