Galactoxyloglucan-doxorubicin nanoparticles exerts superior cytotoxic effects on cancer cells-A mechanistic and in silico approach.
Int J Biol Macromol
; 92: 20-29, 2016 Nov.
Article
en En
| MEDLINE
| ID: mdl-27373427
Galactoxyloglucan (PST001), isolated from seed kernel of Tamarindus indica is a non-toxic immunostimlatory agent with selective cytotoxicity on cancer cells. Toxicity associated with the chemotherapeutic drug doxorubicin (Dox) is the major barrier in its clinical application. Stable, spherically shaped PST-Dox nanoparticles with an average size of 10nm were prepared via ionic gelation of Dox with PST001 which displayed a pH dependent cumulative Dox release kinetics. PST-Dox nanoparticles demonstrated cancer-specific enhanced cytotoxic effects than PST001 and Dox in cancer cells by enhanced cellular uptake of Dox through the induction of apoptosis, sparing normal cells and RBCs. Elucidation of molecular mechanism by whole genome microarray revealed down-regulation of tyrosine kinase oncogenic pathways as PST-Dox mode of action. An in silico model of PST-Dox was developed and computed the activity against topoisomerase IIß, human Abl kinase and protein tyrosine kinases. Computational studies further affirmed the findings of genomic and proteomic investigations with an increased interaction energy between PST-Dox complexes with target system than with Dox and PST001 alone. The important findings and profoundly restrained methodologies highlighted in the current study will accelerate the therapeutic potential of this nanoparticle formulation for substantial clinical studies and testing in several cancers. To conclude, PST-Dox nanoparticles represent a superior drug delivery nanosystem for the effective treatment of cancer even though detailed investigations are warranted.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polisacáridos
/
Doxorrubicina
/
Regulación Neoplásica de la Expresión Génica
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Citotoxinas
/
Nanopartículas
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2016
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Países Bajos