Hydrogel doped with nanoparticles for local sustained release of siRNA in breast cancer

Nathaly Segovia, Maria Pont, Nuria Oliva, Victor Ramos, Salvador Borrós, Natalie Artzi

Producció científica: Article en revista indexadaArticleAvaluat per experts

114 Cites (Scopus)

Resum

Of all the much hyped and pricy cancer drugs, the benefits from the promising siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that would release the drug locally, protect it from degradation, and ensure high transfection efficiency, precludes it from fulfilling its full potential. This work presents a novel platform for local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo in a breast cancer mice model. siRNA protection and high transfection efficiency are enabled by their encapsulation in oligopeptide-terminated poly(β-aminoester) (pBAE) nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced stability of the nanoparticles when embedded in a hydrogel scaffold based on polyamidoamine (PAMAM) dendrimer cross-linked with dextran aldehyde. The combination of oligopeptide-terminated pBAE polymers and biodegradable hydrogels shows improved transfection efficiency in vivo even when compared with the most potent commercially available transfection reagents. These results highlight the advantage of using composite materials for successful delivery of these highly promising small molecules to combat cancer. Oligopeptide-terminated poly(β-aminoester) nanoparticles encapsulating siRNA are incorporated into a hydrogel scaffold based on poly(amido amine) (PAMAM) dendrimer cross-linked with dextran aldehyde. This new novel platform material permits local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo, in a breast cancer mouse model.

Idioma originalAnglès
Pàgines (de-a)271-280
Nombre de pàgines10
RevistaAdvanced Healthcare Materials
Volum4
Número2
DOIs
Estat de la publicacióPublicada - 1 de gen. 2015

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