Folate-targeted multifunctional amino acid-chitosan nanoparticles for improved cancer therapy.
Pharm Res
; 32(2): 562-77, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25186437
ABSTRACT
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, (1)H NMR and DLS. 2D co-culture models were established by using a 12 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
/
Sistemas de Liberação de Medicamentos
/
Quitosana
/
Nanopartículas
/
Ácido Fólico
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Portugal