Improving bleomycin electrochemotherapy with gold nanoparticles: first in vivo study on intra-tumoral field amplification

Electrochemotherapy (ECT) is a cancer treatment approach that utilizes the application of electroporation (EP) with standard chemotherapeutic drugs, resulting in a locally enhanced chemotherapy effect due to enhanced intracellular drug delivery. The aim of this study was to demonstrate (for the first time) that microsecond-range bleomycin electrochemotherapy (1.5 kV/cm × 100 μs × 8 pulses, 1 Hz), when combined with gold nanoparticles (AuNPs, 13 and 46 nm), can be efficiently utilized for in vivo carcinoma tumor treatment. It was anticipated that AuNPs would promote a better treatment response due to local electric field amplification within the tumor as predicted by available in vitro research. We focus the attenuation of tumor progression and reduction of the frequency of metastasis incl. the immune response in the murine BALB/C and 4T1 cancer model. It is shown that the application of 13 nm AuNPs hardly influenced the dynamics of tumor progression (when compared to ECT alone), the synergistic effects are not statistically significant by the end of experiment, which is not the case in vitro. However, the application of 46 nm AuNPs significantly potentiated the efficacy of ECT, which confirms the promising alliance of conductive nanoparticles for local intra-tumoral electric field amplification and ECT.