(EA02-09-25) The Impact of Electroporation on the Therapeutic Efficiency of Colorectal Cancer 3D Printed Cells Under Hypoxia

Scientific conference where the work was recently presented: 5 World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine, and Food & Environmental Technologies

Date on which the work was previously presented at the scientific conference listed: September 15-19, 2024

Objectives: The current study aimed to investigate and evaluate the electroporation efficiency of the therapeutic scheme - standard chemotherapeutic (5-FU) and autophagy inhibitor (chloroquine), alone and in combination, on 3D bioprinted HCT-116 3D cells under normoxic and hypoxic conditions.

Methods: HCT-116 CRC cells were printed with RGD bioink  Drug testing in 3D bioprints was carried out from day 10 to day 13 (for 3 days). Electroporation pulse method: 8 voltage pulses, 100us long, 50Hz with MgCl2/KClEB. Cell viability was assessed with an MTT test.

Results: The study showed that when used in IC₅₀ values in combination, CQ enhances the cell growth inhibitory effect of 5-FU in normal oxygen levels. However, this additive effect is lost when cancer cell 3D-printed aggregates are treated in an extremely hypoxic state. Interestingly, electroporation reverses the drug delivery efficiency and even enhances cell death under hypoxia.

Conclusions: In conclusion, our data demonstrate better drug delivery with electroporation and suggest that electrochemotherapy could lead to more optimal treatment of human CRC cancer 3D cell models. This evidence indicates their potential implementation as a more realistic platform for studying the effect of therapeutics and subsequent application in personalized medicine.

Funding Sources: This study was supported by the Next Generation EU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0007-C01.