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Abstract
Irreversible electroporation (IRE) is an emerging minimally invasive tumor ablation technique that delivers short pulses of strong electric fields and kills cancer cells by disrupting their cell membranes with the electric pulses. However, clinical studies report that more than 10% of local tumor recurrences occur at the original ablated site. NVP BEZ-235 (BEZ) is a dual PI3K/mTOR inhibitor that has substantial anticancer effects. However, the clinical trials of BEZ was not satisfactory because of its low bioavailability and high toxicity, which stemmed from the use of oral administration of high doses over a long period of time. In this research, we prepared a liposomal formulation of BEZ (L-BEZ) for intratumoral injection and studied its antitumor efficacy alone and in combination with IRE. We hypothesized that IRE could release BEZ from the liposomes and that the combination could decrease tumor viability. Our results show that IRE released BEZ from its liposomal encapsulation. The combination of L-BEZ and IRE killed more Hep3B tumor cells in vitro than did L-BEZ or IRE alone and also inhibited cancer cell proliferation in nude mice bearing Hep3B xenografts. Combination of chemotherapeutic agent loaded nanoparticles could enhance the antitumor efficacy of IRE.
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1 Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;
2 College of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA;
3 The University of Texas at Austin Dell Medical School, Austin, TX, USA;
4 McGovern Medical School, Houston, TX, USA;
5 Department of BioSciences, Rice University, Houston, TX, USA;
6 Department of Chemistry, Mississippi State University, Starkville, MS, USA;
7 Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA;
8 Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;; Innovative Nanomedicine Research Unit, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathum Thani, Thailand;
9 Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;
10 Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;; UT Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA