title: Hydrogel doped with nanoparticles for local sustained release of siRNA in breast cancer.
abstract: 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.
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Quimic de Sarrià, Universidad Ramon Llul, Barcelona, 08017, Spain.
authors.forename: Nathaly
authors.initials: N
authors.lastname: Segovia
authors.forename: Maria
authors.initials: M
authors.lastname: Pont
authors.forename: Nuria
authors.initials: N
authors.lastname: Oliva
authors.forename: Victor
authors.initials: V
authors.lastname: Ramos
authors.forename: Salvador
authors.initials: S
authors.lastname: Borrós
authors.forename: Natalie
authors.initials: N
authors.lastname: Artzi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003692:Delayed-Action Preparations; D004952:Esters / Q000737:chemistry; D005260:Female; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry; D014162:Transfection
chemical_list: D003692:Delayed-Action Preparations; D004952:Esters; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008156:Luciferases
keywords: RNAi; breast cancer; hydrogels; nanoparticles; oligopeptide