Activating calcium channels leads to a deadly influx of calcium ions into tumor cells
Calcium ions are essential for cells, but can be toxic in higher
concentrations. A team of researchers has now designed and prepared a
combination drug that kills tumor cells by modulating the calcium influx
into the cell. An external calcium source is not necessary because only
the calcium ions already present in the tumor tissue are used,
according to the study published in the journal Angewandte Chemie.

© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Biological cells need calcium ions, among other things, for the
proper functioning of the mitochondria, the powerhouses of the cells.
However, if there is too much calcium, the mitochondrial processes
become unbalanced and the cell suffocates. A research group led by
Juyoung Yoon of Ewha Womens University in Seoul, South Korea, together
with teams from China, has now taken advantage of this process and
developed a synergistic antitumor drug that can open calcium channels
and thus trigger a deadly calcium storm inside the tumor cell.
The researchers targeted two channels, the first one in the outer
membrane, and the other was a calcium channel in the endoplasmic
reticulum, a cell organelle that also stores calcium ions. The channel
located in the outer membrane opens when it is exposed to a large amount
of reactive oxygen species (ROS), while the channel in the endoplasmic
reticulum is activated by nitric oxide molecules.
To generate the ROS that open the outer membrane calcium channel, the
researchers used the dye indocyanine green. This bioactive agent can be
activated by irradiation with near-infrared light, which not only
triggers reactions that lead to ROS, but it also heats up the
environment. The team explains that the high local temperature activates
the other active agent, BNN-6, to release nitric oxide molecules that
open the channel in the endoplasmic reticulum.
Following successful trials in tumor cell lines, the team tested an
injectable formulation in tumor-implanted mice. To create a
biocompatible combined drug, the researchers loaded the active
ingredients into tiny modified porous silica beads that are not harmful
to 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 observed 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 that received
the preparation.
The authors emphasize that this ion influx approach may also be
useful in related biomedical research areas where a similar mechanism
could activate ion channels different from calcium in order to find new
therapeutic approaches.
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About the Author
Juyoung Yoon is a
Distinguished Professor at the Department of Chemistry and Nano Science
at Ewha Womans University, Seoul, Korea. He is interested in organic
functional and fluorescent materials that can be used in photodynamic
therapy and theranostics, activatable photosensitizers, fluorescent
imaging probes, and photosensors.
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