title: Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of Tetrandrine from a polymeric drug carrier.
abstract: 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.
authors.affiliation: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany; Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Thum
authors.affiliation: Department of Physics, Philipps University Marburg, 35037 Marburg, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Philipps University Marburg, 35037 Marburg, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.affiliation: Department of Physics, Philipps University Marburg, 35037 Marburg, Germany.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelaz
authors.affiliation: Department of Physics, Philipps University Marburg, 35037 Marburg, Germany.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Parak
authors.affiliation: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany. Electronic address: Marc.Schneider@mx.uni-saarland.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014981:Xenopus
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D004337:Drug Carriers; C498655:KCNK9 protein, human; D058185:Magnetite Nanoparticles; D024683:Potassium Channels, Tandem Pore Domain; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C009438:tetrandrine; D019344:Lactic Acid
keywords: Channel inhibitor; Herbal drug; PLGA; Stimulus-responsive; TCM; Temperature triggered