Insight into the cellular uptake mechanism of a secondary amphipathic cell-penetrating peptide for siRNA delivery.
Biochemistry
; 49(16): 3393-402, 2010 Apr 27.
Article
en En
| MEDLINE
| ID: mdl-20302329
Delivery of siRNA remains a major limitation to their clinical application, and several technologies have been proposed to improve their cellular uptake. We recently described a peptide-based nanoparticle system for efficient delivery of siRNA into primary cell lines: CADY. CADY is a secondary amphipathic peptide that forms stable complexes with siRNA and improves their cellular uptake independently of the endosomal pathway. In the present work, we have combined molecular modeling, spectroscopy, and membrane interaction approaches in order to gain further insight into CADY/siRNA particle mechanism of interaction with biological membrane. We demonstrate that CADY forms stable complexes with siRNA and binds phospholipids tightly, mainly through electrostatic interactions. Binding to siRNA or phospholipids triggers a conformational transition of CADY from an unfolded state to an alpha-helical structure, thereby stabilizing CADY/siRNA complexes and improving their interactions with cell membranes. Therefore, we propose that CADY cellular membrane interaction is driven by its structural polymorphism which enables stabilization of both electrostatic and hydrophobic contacts with surface membrane proteoglycan and phospholipids.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
ARN Interferente Pequeño
Aspecto:
Implementation_research
Límite:
Animals
Idioma:
En
Revista:
Biochemistry
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos