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 chemotherapeutic 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 spheroids. 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.
Highlights
Glioblastoma multiforme (GBM) is the most aggressive of all brain tumors, with a median survival of only 15 months after diagnosis.[1]
We describe an in vitro evaluation of a miniaturized capillary fiber-based organic electronic ion pumps (OEIPs) for delivery of Gem, referred to as the gemcitabine ion pump (GemIP), designed to transport, or “pump”, the charged form of the chemotherapeutic Gem through a CEM “ion channel” toward target tumor cells (Figure 1, details Figure S1a–d, Supporting Information)
Similar IC50 curves were obtained with GemIP delivery and manual drug administration (Figure 3a), indicating that GemIPs are a) able to induce GBM cell death via Gem delivery and b) precisely controllable, comparable to manual dosing
Summary
Glioblastoma multiforme (GBM) is the most aggressive of all brain tumors, with a median survival of only 15 months after diagnosis.[1]. OEIP delivery, which comprises electrophoresis through a cation or anion-exchange membrane (CEM or AEM, respectively), ensures that the electronic current precisely corresponds to the ionic (drug) delivery current and provides precise dosage control.[10]. To date, this technology has been successfully applied to the delivery of neurotransmitters in vitro and in vivo,[11] plant hormones,[12,13] and modulators of inflammation in vitro,[14] though not, to our knowledge, to the delivery of anti-cancerous chemotherapeutics. As GemIP operation at 10 nA resulted in efficient delivery rates, we used this setting in all further GBM cell experiments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
