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Title: Dual responsive gelatin-based nanoparticles for enhanced 5-fluorouracil efficiency
Author: Morán Badenas, María del Carmen
Carazo, Javier
Busquets i Viñas, Ma. Antonia
Keywords: Materials nanoestructurats
Citotoxicitat per mediació cel·lular
Nanostructured materials
Cell-mediated cytotoxicity
Issue Date: 13-Sep-2018
Publisher: Elsevier B.V.
Abstract: The very slow progress in the therapeutic efficacy of the treatment of severe diseases has suggested the use of a growing need for a multidisciplinary approach to the delivery of therapeutics to targets tissues. There has been increasing effort in the design of stimuli-responsive nanomaterials that they will be developed into effective drug delivery vehicles. Most commonly, effective drug delivery is associated with nanomaterial-facilitated accumulation and/or cellular internalization. Recent studies in our lab have demonstrated that gelatin-based NPs can be considered suitable pH responsive devices for the effective intracellular delivery of drugs. Concerning cancer treatment, ligands recognizing tumour-associated antigens expressed on the surface of the tumour cells have been employed. Some of the target structures suitable for tumour targeting belong to integrins which mediate cell adhesion to extracellular matrix and other cells. Interestingly, gelatin chains contain motifs such as RGD sequences that can be recognised by integrins. In this work the inclusion of the anticancer drug 5-fluorouracil (5-FU) on these gelatin-based NPs has been projected. These NPs may provide an opportunity to increase the therapeutic effect using a dual approach by: i) targeting the therapeutic drug to the tumour cells by the action of the naturally occurring RGD-motif on gelatin and ii) minimizing the non-productive trafficking from endosomes to lysosomes by releasing the cargo using the charge reversal approach after cellular internalization. In vitro cytotoxicity experiments of NPs on tumoral and non-tumoral cell lines have reported selectivity indexes higher than 30 demonstrating a great selectivity on the mode of action as a function of the cell line and the imposed compositions. Keywords: 5-fluorouracil; Gelatin; In vitro cytotoxicity; Loading efficiency; Nanoparticles; Selectivity. Copyright © 2018 Elsevier B.V. All rights reserved.
Note: Versió postprint del document publicat a:
It is part of: Colloids and Surfaces B-Biointerfaces, 2018, vol. 172, p. 646-654
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ISSN: 0927-7765
Appears in Collections:Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Bioquímica i Fisiologia)

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