Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression
Page view(s)
10
Checked on Dec 08, 2024
Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression
Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression
Ma, P., Luo, Z., Wang, Q., Chen, Y., Liu, F., Ren, C., Wu, C., Li, Z., & Wu, Y.-L. (2024). Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression. Theranostics, 14(8), 3282–3299. https://doi.org/10.7150/thno.94855
Abstract:
Abstract
Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy. The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate. Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance.
Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K+) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K+ channel agonists (Dinitrogen oxide, DZX) and artificial K+ channel molecules (5F8).
Results: Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels on the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway.
Conclusion: The synergistic effect of 5F8 and DZX present more effective in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models. This strategy innovatively integrates antihypertensive drug with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
Grants from external collaborators, including Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, the National Key R&D Program of China, and the Natural Science Foundation of China, as well as the National Natural Science Foundation of China, Shenzhen Science and Innovation Committee.