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

Drug Delivery
Li TianMarites P Melancon

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 en...Continue Reading

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Citations

Feb 9, 2020·International Journal of Molecular Sciences·Chiara TarantelliFrancesco Bertoni
Oct 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li TianMarites P Melancon
Apr 23, 2021·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Raniv D RojoMarites P Melancon
Oct 31, 2020·Cancer Letters·Jian YangHanxiang Zhan

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Methods Mentioned

BETA
dynamic light scattering
xenograft
xenografts

Software Mentioned

SigmaPlot
Aperio eSlide Manager
Aperio ImageScope
Excel

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