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Article Dans Une Revue Pharmaceutical Research Année : 2015

Folate-Targeted Multifunctional Amino Acid-Chitosan Nanoparticles for Improved Cancer Therapy

Résumé

URPOSE : Tumor targeting nanomaterials have potential for improving the efficiency of anti-tumoral therapeutics. However, the evaluation of their biological performance remains highly challenging. In this study we describe the synthesis of multifunctional nanoparticles decorated with folic acid-PEG and dual amino acid-modified chitosan (CM-PFA) complexed with DNA and their evaluation in organotypic 2D co-cultures of cancer-normal cells and also on 3D multicellular tumor spheroids models. METHODS : The physicochemical characterization of CM-PFA multifunctional carriers was performed by FTIR, 1H NMR and DLS. 2D co-culture models were established by using a 1:2 cancer-to-normal cell ratio. 3D organotypic tumor spheroids were assembled using micromolding technology for high throughput screening. Nanoparticle efficiency was evaluated by flow cytometry and confocal microscopy. RESULTS : The CM-PFA nanocarriers (126-176 nm) showed hemocompatibility and were internalized by target cells, achieving a 3.7 fold increase in gene expression. In vivo-mimicking 2D co-cultures confirmed a real affinity towards cancer cells and a negligible uptake in normal cells. The targeted nanoparticles penetrated into 3D spheroids to a higher extent than non-targeted nanocarriers. Also, CM-PFA-mediated delivery of p53 tumor suppressor promoted a decrease in tumor-spheroids volume. CONCLUSION : These findings corroborate the improved efficiency of this delivery system and demonstrate its potential for application in cancer therapy.
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Dates et versions

hal-01171243 , version 1 (03-07-2015)

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Vítor M. Gaspar, Elisabete C. Costa, João A. Queiroz, Chantal Pichon, Fani Sousa, et al.. Folate-Targeted Multifunctional Amino Acid-Chitosan Nanoparticles for Improved Cancer Therapy. Pharmaceutical Research, 2015, 32 (2), pp.562-577. ⟨10.1007/s11095-014-1486-0⟩. ⟨hal-01171243⟩
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