Speaker
Description
Gelonin is a ribosome-inactivating protein with high intracellular toxicity but limited cell permeability. Targeted membrane disruption, such as electroporation, enhances its cellular uptake for potential cancer therapy and tissue ablation. We demonstrate a 100- to 1,000-fold increase in gelonin cytotoxicity with pulsed electric fields in T24, U-87, and CT26 cell lines. The effective gelonin concentration for 50% cell killing (EC50) ranged from <1 nM to ~100 nM in electroporated cells, whereas intact cells showed minimal response even at 1,000 nM, reducing survival by only 5–15%.
Longer pulses proved more effective at lowering gelonin EC50 across isoeffective electroporation protocols using 300-ns, 9-µs, and 100-µs pulses. Increasing the electric field strength of eight 100-µs pulses from 0.65 to 1.25 kV/cm further reduced EC50 from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cytotoxicity. These findings highlight the potential of pulsed electric field-mediated gelonin delivery for tumor and hyperplasia ablation at low concentrations, minimizing systemic toxicity.
