2024-03-28T20:15:02Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/57052021-11-02T12:01:27Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
00925njm 22002777a 4500
dc
Tapia, Lucía
author
Pérez, Yolanda
author
Bolte, Michael
author
Casas, Josefina
author
Solà, Jordi
author
Quesada Pato, Roberto
author
Alfonso, Ignacio
author
2019-09
Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage‐like anionophores displaying pH‐dependent activity. When protonated, they efficiently bind chloride anions. They also transport chloride through lipid bilayers, with their anionophoric properties improving at acidic pH, suggesting an H+/Cl− symport mechanism. NMR studies in DPC micelles demonstrate that the cages bind chloride within the lipid phase. The chloride affinity and the chloride‐exchange rate with the aqueous bulk solution are improved when the pH is lowered. This increases cytotoxicity towards lung adenocarcinoma cells at the pH of the microenvironment of a solid tumor. These properties depend on the nature of the amino‐acid side chains of the cages, which modulate their lipophilicity and interactions with the cell membrane. This paves the way towards using pH as a parameter to control the selectivity of cytotoxic ionophores as anticancer drugs.
1433-7851
http://hdl.handle.net/10259/5705
10.1002/anie.201905965
1521-3773
pH‐dependent chloride transport by pseudopeptidic cages for the selective killing of cancer cells in acidic microenvironments