Antitumor Efficacy of Irreversible Electroporation and Doxorubicin-Loaded Polymeric Micelles

Irreversible electroporation (IRE) is a novel non-thermal ablative treatment for cancer patients with unresectable tumor. IRE kills tumor cells by applying a strong electric field across the cell membrane, thereby creating irreparable pores. Compared to conventional thermal ablation, IRE is effective in perivascular tissues and can preserve the surrounding sensitive structures. However, tumor cells may survive in the regions exposed to insufficient electric field strength, and cause tumor relapse afterwards. We prepared a doxorubicin-loaded polymeric micelles system (M-Dox) using oil-in-water emulsion. The resultant M-Dox was 37.9 ± 3.2 nm in size with a Dox loading of 4.3% by weight. M-Dox is toxic to multiple human cancer cell lines with IC50 values in nanomolar and micromolar range. When combined with IRE in a hepatic carcinoma mouse xenograft model, the tumor treated with the combination therapy (IRE + M-Dox) was the highest in both M-Dox uptake and percentage of necrosis. Immunohistochemical staining also confirmed that the fewest proliferating cells were present after the combination therapy. Our data suggested that M-Dox was an effective adjuvant treatment to enhance the anti-tumor efficacy of IRE.