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Pharm Dev Technol. 2020 Apr;25(4):408-415. doi: 10.1080/10837450.2019.1705485. Epub 2019 Dec 27.

Development and characterization of CD73-siRNA-loaded nanoemulsion: effect on C6 glioma cells and primary astrocytes.

Author information

1
Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, UFPEL, Pelotas, Brazil.
2
Grupo de Pesquisa em Nanobiotecnologia e Nanotoxicologia, UNIPAMPA, Uruguaiana, Brazil.
3
Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil.
4
Departamento de Genética Médica, Escola de Medicina, UNICAMP, Campinas, Brazil.
5
Departamento de Morfologia, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, Brazil.
6
Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, Canada.
7
Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
8
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, Brazil.
9
Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Porto Alegre, Brazil.

Abstract

Introduction: Glioblastoma (GB) is the most common malignant brain tumor and is characterized by high invasiveness, poor prognosis, and limited therapeutic options. Silencing gene expression, through the use of small interfering RNA (siRNA), has been proposed as an alternative to conventional cancer therapy. Here, we evaluated the potential of CD73 as a new therapeutic target, since it is overexpressed in solid tumors and has emerged as a promising target to control GB progression.Methods: A cationic nanoemulsion (NE) as an intravenous siRNA-CD73 delivery system was developed and its effect on C6 glioma cell viability was determined.Results: The nanostructured system was effective in complexing oligonucleotides for delivery to target cells. In addition, we observed that the NE-siRNA-CD73 complex was effective in reducing CD73 protein levels and AMPase activity, which were related to decreased C6 glioma cell viability.Conclusions: These findings indicate the potential of siRNA-CD73-loaded cationic NE as a therapeutic alternative for glioma treatment.

KEYWORDS:

CD73; Glioblastoma; cationic nanoemulsion; drug delivery; ecto-5′-nucleotidase; siRNA

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