Nanoemulsion formulation of a novel taxoid DHA-SBT-1214 inhibits prostate cancer stem cell-induced tumor growth.

Autor: Ahmad G; Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115-5000, USA., El Sadda R; Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, 11794-3400, USA., Botchkina G; Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, 11794-3400, USA; Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, NY, 11794-8691, USA., Ojima I; Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, 11794-3400, USA; Department of Chemistry, Stony Brook University, Stony Brook, NY, 11794-3400, USA., Egan J; Targagenix, Inc., 25 Health Sciences Drive, Stony Brook, NY, 11790-3382, USA., Amiji M; Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115-5000, USA. Electronic address: m.amiji@northeastern.edu.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2017 Oct 10; Vol. 406, pp. 71-80. Date of Electronic Publication: 2017 Aug 11.
DOI: 10.1016/j.canlet.2017.08.004
Abstrakt: The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane ® and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells. Qualitative intracellular uptake studies of dye encapsulated NEs by confocal imaging showed uptake by both monolayer and spheroid cultured PPT2 cells. Treatment of PPT2 cells with NE DHA-SBT-1214 (1nM-1μM for monolayer culture of cells grown on collagen-coated dishes for 48 h) induced complete cell death, showing higher efficacy as compared to the drug solution. This nanoemulsion (10nM-10μM) also showed toxicity in 3D culture of floating spheroids. Weekly intravenous administration of the NE-DHA-SBT-1214 to NOD/SCID mice bearing subcutaneous PPT2 tumor xenografts led to dramatic suppression of tumor growth compared to Abraxane ® and placebo nanoemulsion formulation. Viable cells that survived from this in vivo treatment regimen were no longer able to induce floating spheroids and holoclones, whereas control and Abraxane ® treated tumor cells induced a large number of both. The results show that NE-DHA-SBT-1214 possesses significant activity against prostate CD133 high /CD44+/ high tumor-initiating cells both in vitro and in vivo.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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