Activation of calcium channels leads to lethal influx of calcium ions into tumor cells. Calcium ions play a critical role in cellular functions but can become harmful at high levels. Researchers recently developed a compound that targets and destroys tumor cells by regulating the influx of calcium into the cell. This innovative approach eliminates the need for an external calcium source by using calcium ions already present in the tumor tissue. The results of this study are detailed in an article published in the journal. Angewandte Chemie.

Biological cells require calcium ions, among other things, for the proper functioning of mitochondria, the cells’ power plants. However, if there is too much calcium, mitochondrial processes become unbalanced and the cell becomes overwhelmed. A research team led by Juen Yun of Ewha Women’s University in Seoul, South Korea, along with teams from China, took advantage of this process and developed a synergistic anti-tumor drug that can trigger a deadly calcium storm by opening calcium channels. inside the body. tumor cell.

Mechanism of antitumor drug

The researchers targeted two channels, one in the outer membrane and the other a calcium channel in the endoplasmic reticulum, a cell organelle that stores calcium ions. The channel located in the outer membrane opens when exposed to large amounts of reactive oxygen species (ROS), while the channel in the endoplasmic reticulum is activated by nitric oxide molecules.

The researchers used the dye indocyanine green to generate ROS, which opens the outer membrane’s calcium channel. This biologically active substance can be activated by irradiation with near-infrared light; this not only triggers reactions that lead to ROS, but also heats up the environment. The team explains that high local temperature activates another active substance, BNN-6, to release nitric oxide molecules, which open a channel in the endoplasmic reticulum.

After successful trials on tumor cell lines, the team tested the injectable formulation on tumor-implanted mice. To create a biocompatible combination drug, the researchers loaded the active ingredients into modified small porous silica beads that do not harm the body but can be recognized by tumor cells and transported into the cell. After injecting the beads into the bloodstream of the mice, the researchers noticed that the drug accumulated in the tumor. Exposure to near-infrared light successfully triggered the mechanism of action, and the tumor disappeared after a few days in mice receiving the drug.

The authors emphasize that this approach to ion flow could also be useful in related areas of biomedical research, where a similar mechanism could activate ion channels other than calcium channels to find new therapeutic approaches.