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Orientador(es)
Resumo(s)
Purpose
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.
Descrição
Palavras-chave
Cancer therapy Gene delivery Targeted nanoparticles 2D co-cultures 3D tumor spheroids
Contexto Educativo
Citação
Gaspar, V.M., Costa, E.C., Queiroz, J.A., Pichon, C., Sousa, F. e Correia, I.J. (2015) “Folate-Targeted Multifunctional Amino Acid-Chitosan Nanoparticles for Improved Cancer Therapy”, Pharmaceutical Research, Vol. 32(2): pp. 562-577
Editora
Springer