Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

João Conde, Nuria Oliva, Mariana Atilano, Hyun Seok Song, Natalie Artzi

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218 Cites (Scopus)

Resum

The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs - a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor) - provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.

Idioma originalAnglès
Pàgines (de-a)353-363
Nombre de pàgines11
RevistaNature Materials
Volum15
Número3
DOIs
Estat de la publicacióPublicada - 1 de març 2016
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