Targeted Chemotherapy of Glioblastoma Spheroids with an Iontronic Pump

Abstract

Successful treatment of glioblastoma multiforme (GBM), the most lethal tumor of the brain, is presently hampered by (i) the limits of safe surgical resection and (ii) "shielding" of residual tumor cells from promising chemo-therapeutic drugs such as Gemcitabine (Gem) by the blood brain barrier (BBB). Here, the vastly greater GBM cell-killing potency of Gem compared to the gold standard temozolomide is confirmed, moreover, it shows neuronal cells to be at least 104-fold less sensitive to Gem than GBM cells. The study also demonstrates the potential of an electronically-driven organic ion pump ("GemIP") to achieve controlled, targeted Gem delivery to GBM cells. Thus, GemIP-mediated Gem delivery is confirmed to be temporally and electrically controllable with pmol min−1 precision and electric addressing is linked to the efficient killing of GBM cell monolayers. Most strikingly, GemIP-mediated GEM delivery leads to the overt disintegration of targeted GBM tumor sphe-roids. Electrically-driven chemotherapy, here exemplified, has the potential to radically improve the efficacy of GBM adjuvant chemotherapy by enabling exquisitely-targeted and controllable delivery of drugs irrespective of whether these can cross the BBB.