Combination therapy comprising irreversible electroporation and hydroxycamptothecin loaded electrospun membranes to treat rabbit VX2 subcutaneous cancer

Irreversible electroporation (IRE) is a kind of promising cancer treatment technology. However, local recurrence still occurs because of incomplete ablation. The aim of this study was to investigate the combined therapy of IRE and a hydroxycamptothecin loaded electrospun membrane (EM/HCPT) to treat rabbit VX2 subcutaneous cancer. HCPT loaded membranes were developed by electrospinning. Mechanical test and in vitro drug release study of EM/HCPT were performed. 24 rabbits with subcutaneous VX2 tumor were randomly divided into four groups: the control group, the EM/HCPT group, the IRE ablation group, and the IRE + EM/HCPT group. The tumor cells were ablated by IRE first, followed by subcutaneous implantation of EM/HCPT to release HCPT constantly in order to damage the residual cancer cells. The tumor inhibition efficacy was assessed by the tumor real-time monitoring, histological and immunofluorescent analyses, and transmission electron microscopy (TEM) examination. Assessment of the release from EM/HCPT showed that HCPT release lasted for about 7 days. The in vivo antitumor efficacy assessment, histological and immunofluorescent analyses, and TEM examination showed that IRE + EM/HCPT had the best tumor inhibition ability. In addition, the biochemical analyses and hematoxylin and eosin (H&E) staining of normal organs indicated that IRE + EM/HCPT treatment was safe. Our study provided a new concept in cancer treatment and might promote the application of IRE.