Self-Assembled Oleic Acid-Modified Polyallylamines for Improved siRNA Transfection Efficiency and Lower Cytotoxicity.
ACS Appl Bio Mater
; 6(2): 529-542, 2023 02 20.
Article
en En
| MEDLINE
| ID: mdl-36647574
ABSTRACT
Small interference RNA (siRNA) is a tool for gene modulation, which can silence any gene involved in genetic disorders. The potential of this therapeutic tool is hampered by RNA instability in the blood stream and difficulties to reach the cytosol. Polyamine-based nanoparticles play an important role in gene delivery. Polyallylamine hydrochloride (PAH) is a polycation displaying primary amines that can be easily chemically modified to match the balance between cell viability and siRNA transfection. In this work, PAH has been covalently functionalized with oleic acid at different molar ratios by carbodiimide chemistry. The substituted polymers form polyplexes that keep positive surface charge and fully encapsulate siRNA. Oleic acid substitution improves cell viability in the pulmonary cell line A549. Moreover, 6 and 14% of oleic acid substitution show an improvement in siRNA transfection efficiency. CD47 is a ubiquitous protein which acts as "don't eat me signal." SIRPα protein of macrophages recognizes CD47, leading to tumor cell phagocytosis by macrophages. By knocking down CD47 with siRNA, cancer cells become vulnerable to be eliminated by the immune system. PAH-oleic acid substitutes show high efficacy in silencing the CD47 protein, making them a potential candidate for immunotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácido Oléico
/
Antígeno CD47
Idioma:
En
Revista:
ACS Appl Bio Mater
Año:
2023
Tipo del documento:
Article
País de afiliación:
España