Scientists have developed a new anti-tumor drug that induces a lethal influx of calcium ions in tumor cells by targeting specific channels. This innovative approach utilizes existing calcium ions in tumors and was successfully tested in mice, providing a potential new approach to cancer treatment.
Calcium ions play a vital role in cell function, but if levels are too high, they can be harmful to cells. Researchers recently developed a compound that can target and destroy tumor cells by regulating the influx of calcium ions within cells. This innovative approach utilizes calcium ions already within the tumor tissue, eliminating the need for an external calcium source. A paper published in the journal Angewandte Chemie details the findings.
Biological cells require calcium ions to maintain the normal functioning of mitochondria, the powerhouses of the cell. However, if there are too many calcium ions, mitochondrial processes become unbalanced and the cell suffocates. A research team led by Juyoung Yoon of Ewha Womans University in Seoul, South Korea, together with a team from China, used this process to develop a synergistic anti-tumor drug that opens calcium ion channels to trigger a deadly calcium ion storm within tumor cells.
The researchers targeted two channels, the first one in the outer membrane and the other a calcium channel in the endoplasmic reticulum, an organelle that also stores calcium ions. Channels located in the outer membrane open upon exposure to large amounts of reactive oxygen species (ROS), while channels in the endoplasmic reticulum are activated by nitric oxide molecules.
To generate ROS that open outer membrane calcium channels, the researchers used the dye indocyanine green. This bioactive agent can be activated by near-infrared irradiation, which not only triggers reactions that lead to ROS, but also heats the environment. The team explains that local high temperatures activate another active agent, BNN-6, to release nitric oxide molecules, which open channels in the endoplasmic reticulum.
After successful trials with tumor cell lines, the team tested an injectable formulation in mice with implanted tumors. To create a biocompatible drug combination, the researchers packed the active ingredients into tiny modified porous silica beads that are harmless to the body but can be recognized by tumor cells and transported into the cells. After injecting the beads into the bloodstream of mice, the researchers observed the drug accumulating within the tumors. Irradiation of near-infrared light successfully triggered the mechanism of action, and tumors in mice that received this preparation disappeared after a few days.
The authors emphasize that this ion influx method may also be applicable to related biomedical research fields, because similar mechanisms can activate ion channels different from calcium ion channels, thereby finding new treatments.
Compiled source: ScitechDaily