Fibronectin-adherent peripheral blood derived mononuclear cells as Paclitaxel carriers for glioblastoma treatment: An in vitro study

Roberto Pallini, Giulio Alessandri, Marco Paolo Schiariti, Francesco Restelli, Paolo Ferroli, Anna Benetti, Angiola Berenzi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Moris Cadei, Gaetano Finocchiaro, Augusto Pessina, Eugenio Parati

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

5 Citazioni (Scopus)

Abstract

Background: Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. Methods: MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients. MCs were cultured and the adherent population on fibronectin (FN-MCs), after immunocytochemistry and flow cytometry characterization, was loaded with Paclitaxel (FN-MCs-PTX). Antiproliferative and migration activity of FN-MCs-PTX was evaluated in two-dimensional (2D) and three-dimensional (3D) co-culture assays with red fluorescent U87 Malignant Glioma cells and primary GBM cells. Antiangiogenic properties of FN-MCs-PTX were tested on cultures with endothelial cells. Results: Phenotypical characterization showed a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in vitro (P <. 0.01). Moreover, tumor-induced migration of MCs, although partially affected by the PTX cargo, remained statistically significant when compared with unprimed cells and this was confirmed in a 3D Matrigel model (P <. 0.01) and in a Trans-well assay (P <. 0.01). FN-MCs-PTX also disclosed considerable antiangiogenic properties. Discussion: Our results suggest that the fibronectin-adherent population of MCs isolated from peripheral blood can be an effective tool to inhibit GBM growth. Given the relative facility to obtain such cells and the short time needed for their culture and drug loading this approach may have potential as an adjuvant therapy for GBM.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaCytotherapy
Volume2017
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Cancer Research
  • Cell Biology
  • Drug delivery
  • Genetics (clinical)
  • Glioblastoma
  • Immunology
  • Immunology and Allergy
  • Mononuclear cells
  • Oncology
  • Paclitaxel
  • Transplantation

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