1.D.250. The Amphiphilic Mitochondrial Targeting Polymer (TMP) Carrier (TMP-C) Family
Pharmacological targeting of mitochondrial ion channels may provide a new direction in cancer therapy (Ma et al. 2024). 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. Ma et al. 2024 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). Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels in the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Thus,the synergistic effect of 5F8 and DZX presents greater effectiveness 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 drugs with artificial ion channel molecules to inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis (Ma et al. 2024).