Antitumor Efficacy of Irreversible Electroporation and Doxorubicin-Loaded Polymeric Micelles

Irreversible electroporation (IRE), a nonthermal ablative treatment for unresectable tumors, applies an electrical field across the cell membrane, creating irreparable pores. Compared with conventional thermal ablation, IRE can preserve nearby structures. However, tumors may recur in regions exposed to insufficient electrical field strength. We developed a novel doxorubicin-loaded polymeric micelle system (M-Dox) using oil-in-water emulsion. M-Dox particles were 37.9 nm +/- 3.2 nm in diameter, with 4.3% Dox loading by weight. M-Dox was toxic to four human cancer cell lines at nanomolar and micromolar median inhibitory concentrations. We used a hepatic carcinoma xenograft mouse model to evaluate the antitumor efficacy of M-Dox and IRE. Tumors treated with IRE + M-Dox had the highest M-Dox uptake and percentage of necrotic cells, compared with the monotherapy and control groups. Immunohistochemical staining confirmed that the combination group had the fewest proliferating cells. Our data suggest that adjuvant M-Dox enhanced the antitumor efficacy of IRE.