Insights into the Development of an Iontronic Tunable Chemoimmunotherapy System

Franciska Telebar-Žbulj^a, Vito Telebar-Žbulj^a^,^c, Helena Saarela^b, Iwona Bernacka Wojcik^b, Johannes Bintinger^b, Theresia Arbring Sjöström^b, Julia Kargl^c, Daniel Simon^b, Rainer Schindl^a, Linda Waldherr^a

^aMedical University of Graz, Chair of Biophysics, Neue Stiftingtalstraße, 6, Graz, Austria

^bLaboratory of Organic Electronics, Linköping University, Sweden, Bredgatan, 33, Norrköping, Sweden

^cOtto Loewi Research Center - Immunology and Pathophysiology, Medical University of Graz

Materials for Sustainable Development Conference (MATSUS)
Proceedings of MATSUS Fall 2023 Conference (MATSUSFall23)

#BIOEL - Bioelectronics

Torremolinos, Spain, 2023 October 16th - 20th

Organizers: Francesca Santoro and Achilleas Savva

Poster, Franciska Telebar-Žbulj, 173
Publication date: 18th July 2023

Introduction: We use ELectroPHoretic Implants (ELPHIs) for triggered drug release of transiently charged chemotherapeutics, which rely on a precise and electronically controllable drug delivery mechanism. The used devices allow long-lasting device durability and precise electrical control over delivery rates. Continuous ELPHI-mediated gemcitabine administration efficiently reduces tumor size compared to drop casting, maintaining a high local drug concentration over 24 hours. Building on this success, we plan to translate this progress into implantable ELPHI device designs for in vivo studies using established technology for combination therapies such as chemoimmunotherapy.

Aim: We aim to develop a powerful multi-level cancer treatment system using an in vivo implant. This system will synergize the local tumor-reducing effects achieved by the controlled long-term release of potent chemotherapeutics via ELPHI. By utilizing timed, high drug concentrations for efficient local tumor shrinkage, our goal is to decrease tumor size, improve overall survival, and reduce tumor recurrence and tumor antigen presentation.

Methods: Implantation of a chemo-ELPHI in a mouse flank will be followed by foreign body response (FBR) measurement using immunohistochemistry (IHC) and flow cytometry. We use a mouse model that offers a controlled immune response and inject tumor cells near the ELPHI implant site, followed by chemo-ELPHI treatment. Pharmacokinetic studies utilizing LC-MS will assess implant performance and optimize drug concentrations locally while minimizing systemic effects.

Expected Results: With the respected methods, we can estimate the FBR and implant performance. These are essential steps to build up towards the combinational treatment with immune checkpoint inhibitors- which has the potential to treat tumors both locally and distally.

References:

[1] Waldherr, L., Seitanidou, M., Jakešová, M., Handl, V., Honeder, S., Nowakowska, M., Tomin, T., Karami Rad, M., Schmidt, T., Distl, J., Birner‐Gruenberger, R., von Campe, G., Schäfer, U., Berggren, M., Rinner, B., Asslaber, M., Ghaffari‐Tabrizi‐Wizsy, N., Patz, S., Simon, D. T., & Schindl, R. (2021). Targeted Chemotherapy of Glioblastoma Spheroids with an Iontronic Pump. Advanced Materials Technologies, 6(5), 2001302.

[2] Simon, D. T., Kurup, S., Larsson, K. C., Hori, R., Tybrandt, K., Goiny, M., Jager, E. W. H., Berggren, M., Canlon, B., & Richter-Dahlfors, A. (2009). Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function. Nature Materials, 8(9), 742–746.

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