Kinetically Controlled Polyelectrolyte Complex Assembly of microRNA-Peptide Nanoparticles toward Treating Mesothelioma.
Adv Mater
; 36(24): e2314367, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38532642
ABSTRACT
Broad size distributions and poor long-term colloidal stability of microRNA-carrying nanoparticles, especially those formed by polyelectrolyte complexation, represent major hurdles in realizing their clinical translation. Herein, peptide design is used alongside optimized flash nanocomplexation (FNC) to produce uniform peptide-based miRNA particles of exceptional stability that display anticancer activity against mesothelioma in vitro and in vivo. Modulating the content and display of lysine-based charge from small intrinsically disordered peptides used to complex miRNA proves essential in achieving stable colloids. FNC facilitates kinetic isolation of the mechanistic steps involved in particle formation to allow the preparation of particles of discrete size in a highly reproducible, scalable, and continuous manner, facilitating pre-clinical studies. To the best of the authors knowledge, this work represents the first example of employing FNC to prepare polyelectrolyte complexes of miRNA and peptide. Encapsulation of these particles into an injectable hydrogel matrix allows for their localized in vivo delivery by syringe. A one-time injection of a gel containing particles composed of miRNA-215-5p and the peptide PKM1 limits tumor progression in a xenograft model of mesothelioma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
MicroARNs
/
Nanopartículas
/
Mesotelioma
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Mater
Asunto de la revista:
BIOFISICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos