Williams Cancer Institute

GROUNDBREAKING ADVANCEMENTS IN CANCER TREATMENT: SYNERGISTIC DRUG TARGETING CALCIUM FLOW

GROUNDBREAKING ADVANCEMENTS IN CANCER TREATMENT: SYNERGISTIC DRUG TARGETING CALCIUM FLOW


In the realm of medical research, a team of scientists has achieved a significant breakthrough by designing a combined drug capable of eliminating tumor cells by modulating calcium flow within the cells. This innovative approach circumvents the need for an external source of calcium, utilizing only the calcium ions present in the tumor tissue, as revealed by a study published in the journal Angewandte Chemie International Edition.

Calcium ions are essential for cellular function, but their accumulation in elevated concentrations can be toxic. Imbalances in mitochondrial processes due to excess calcium can lead to cellular suffocation.

Led by Juyoung Yoon from Ewha Womens University in Seoul, South Korea, in collaboration with Chinese teams, the group capitalized on this process to develop a synergistic anti-tumor drug capable of opening calcium channels and triggering a lethal calcium storm within the tumor cell.

They targeted two channels, one in the outer membrane and another in the endoplasmic reticulum, a cellular organelle that stores calcium ions. The channel in the outer membrane activates in the presence of a substantial amount of reactive oxygen species (ROS), while the channel in the endoplasmic reticulum responds to nitric oxide molecules.

To generate ROS that open the calcium channel in the outer membrane, researchers used the dye indocyanine green. This bioactive agent is activated by near-infrared light irradiation, inducing reactions that generate ROS and increase local temperature. The elevated temperature activates another active agent, BNN-6, releasing nitric oxide molecules that open the channel in the endoplasmic reticulum.

After successful trials in tumor cell lines, the team tested an injectable formulation in mice with implanted tumors. To create a biocompatible combined drug, they loaded active ingredients into tiny modified porous silica beads that are non-harmful to the body but recognized and transported by tumor cells.

After injection into the mice’s bloodstream, the researchers observed drug accumulation in the tumor. Exposure to near-infrared light successfully triggered the mechanism of action, resulting in tumor disappearance after a few days in treated mice.

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 to explore new therapeutic approaches. This achievement represents a promising step toward the development of more specific and effective cancer treatments.

Link: https://medicalxpress.com/news/2024-01-combination-drug-calcium-channels-trigger.html
https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202317578

Reference: Hu, J.-J., Yuan, L., Zhang, Y., Kuang, J., Song, W., Lou, X., Xia, F., & Yoon, J. (2024). Photo‐controlled calcium overload from endogenous sources for tumor therapy. Angewandte Chemie (International Ed. in English). https://doi.org/10.1002/anie.202317578

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