Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of Tetrandrine from a polymeric drug carrier.

Two-pore domain (K2P) potassium channels have recently attracted growing interest in the field of cancer research. These channels play an important role in cancer biology specifically for cancer progression, including proliferation, migration, and apoptosis, which makes them an attractive target for novel cancer therapies. Here, we examined the effect of Tetrandrine (Tet), a natural compound known as a channel modulator, which is associated with anticancer activities, as potential drug in this regard. Xenopus oocyte with overexpression of K2P 9.1 (TASK 3) channels has been chosen as model system for this purpose. In order to release Tet and trigger the channels we developed a polymeric magnetic delivery system: Tetrandrine-Magnetite co-loaded poly (lactic-co-glycolic) acid particles. The embedded iron oxide magnetite (Fe3O4) nanoparticles (NPs) allow to inductively heat the particles by applying a high frequency alternating magnetic field, and thus trigger the release of the co-encapsulated Tet. As a proof of concept the nanoparticulate drug delivery system was heated by raising the suspension's temperature proving the temperature dependent release behaviour. Both heating approaches were then successfully applied for measuring the TASK 3 channels current in response to the released drug. It was found that the released Tet amount is sufficient to inhibit the TASK 3 channels in a dose dependent manner. Thus, such a stimulus responsive drug delivery system holds great promise as a novel approach for the treatment of various cancer types such as for the interaction with the two-pore domain potassium channels K2P 9.1.