Antitumor efficacy of liposome-encapsulated NVP-BEZ 235 in combination with irreversible electroporation

Drug Delivery

Patrick Lee¹  Saisree Ravi²  Jun Zhao³  Linfeng Lu⁴  Thomas A. Rogers⁵  Li Tian⁶  Yang Qiao⁶  Burapol Singhana⁷  Marites P. Melancon⁸  Ashley Chang⁹  Lucas Wang^1,10 

[1] College of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA;Department of BioSciences, Rice University, Houston, TX, USA;Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA;Department of Chemistry, Mississippi State University, Starkville, MS, USA;Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;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;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, US;McGovern Medical School, Houston, TX, USA;The University of Texas at Austin Dell Medical School, Austin, TX, USA;

关键词: Nanoparticles;    liposomes;    irreversible electroporation (IRE);    combination therapy;    cancer;    hepatocellular carcinoma;    drug delivery;    NVP BEZ-235;   

DOI  :  10.1080/10717544.2018.1444683

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY