EGFR-targeted immunoliposomes as a selective delivery system of simvastatin, with potential use in treatment of triple-negative breast cancers.

Autor: Matusewicz L; Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, ul. F. Joliot-Curie 14a, 50-383 Wroclaw, Poland., Filip-Psurska B; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wroclaw, Poland., Psurski M; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wroclaw, Poland., Tabaczar S; Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, ul. F. Joliot-Curie 14a, 50-383 Wroclaw, Poland., Podkalicka J; Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, ul. F. Joliot-Curie 14a, 50-383 Wroclaw, Poland., Wietrzyk J; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wroclaw, Poland., Ziółkowski P; Department of Pathology, Wroclaw Medical University, ul. K. Marcinkowskiego 1, 50-368 Wroclaw, Poland., Czogalla A; Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, ul. F. Joliot-Curie 14a, 50-383 Wroclaw, Poland., Sikorski AF; Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, ul. F. Joliot-Curie 14a, 50-383 Wroclaw, Poland. Electronic address: aleksander.sikorski@uwr.edu.pl.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2019 Oct 05; Vol. 569, pp. 118605. Date of Electronic Publication: 2019 Aug 07.
DOI: 10.1016/j.ijpharm.2019.118605
Abstrakt: A promising strategy for treatment of EGFR-dependent tumours is EGFR signal transduction suppression via inhibition of HMG-CoA reductase using high doses of statins, popular cholesterol-lowering drugs. The main purpose of this study was to obtain targeted long circulating immunoliposomes containing simvastatin (tLCLS) with anti-EGFR antibody attached to their surface and to test whether they can be effective in treatment of TNBC. The designed tLCLS were characterized in terms of physicochemical properties and long-term stability. In vitro experiments conducted on MDA-MB-231 cells demonstrated that tLCLS induced apoptosis and are characterized by IC 50 of 7.5 µM. Treatment of studied cells with tLCLS led to a decrease in membrane order and inhibited PI3K/Akt signalling. Analyses of efficacy of the tLCLS in in vivo experiments in model animals indicate that immunoliposomes were effectively delivered to tumours. Our results showed that regardless of whether tLCLS were administered before or after tumour formation, at the tested dose they inhibited tumour growth by an average of 25% in comparison to the control. However, the results were not statistically significant. The experiments described above allowed us to test the possibility of using immunoliposomes as simvastatin carriers delivering increased amounts of the drug to tumour cells.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: