Many chemotherapeutic agents are limited in their success in cancer treatment due to poor delivery and systemic toxicity. A way to efficiently interfere with cancer growth and to reduce tumor recurrence is local chemotherapy. This is especially of interest for the treatment of high grade brain tumors, which remain an unmastered clinical challenge due to high recurrence rates and frequently occurring resistance to standard chemotherapeutics.

We present miniature organic electronic devices for drug delivery able to administer chemotherapeutics via electric control with high spatiotemporal precision.¹  Incorporated in these devices are anionic hyperbranched polyglycerol membranes, forming an ion selective matrix of multiple fixed negative charges.² Through this polymeric membrane, drugs electromigrate in an electric field towards a target of choice. Here, a free-standing capillary prototype was used for proof-of-principle experiments.

The performance of these bioelectronic devices, called chemotherapeutic ion pumps (chemoIPs),  was characterized with voltammetric and amperometric measurements and tested in different brain tumor models with increasing complexity (cell culture to short-term in vivo model). ChemoIP-mediated drug delivery was compared to computer simulations. Additionally, the influence of Gem on neural and cancerous brain cultures was analyzed with whole proteome analysis. The treatment efficiency was analyzed based on cell death, suppression of tumor growth and drug distribution.

ChemoIPs enable drug delivery with pmol*min^-1 precision at currents in the nano-ampere range. The further application of this electrical and temporal control was shown in the cell monolayer and 3D cell culture, triggering the disintegration of targeted brain tumor spheroids among chemoIP treatment. Via whole proteome and cell viability analysis we confirmed that Gem efficiently kills brain tumor cells, while neuronal cultures are unaffected. Additionally, we show preliminary results indicating that the chemoIP treatment significantly induces tumor shrinkage in a short-term in vivo brain tumor model.

The here exemplified electrically-driven drug delivery via chemoIPs is a drug administration method that can serve as basis for further implant development, which has the potential to increase the efficacy of chemotherapy due to highly-targeted and locally-controlled drug delivery.