title: Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment.
abstract: 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.
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK.
authors.forename: João
authors.identifier: http://orcid.org/0000-0001-8422-6792
authors.initials: J
authors.lastname: Conde
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Nuria
authors.initials: N
authors.lastname: Oliva
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Grup d'Enginyeria de Materials, Institut Químic de Sarrià-Universitat Ramon Llull, Barcelona 08017, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Atilano
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Division of Bioconvergence Analysis, Korea Basic Science Institute, Yuseong, Daejeon 169-148, Republic of Korea.
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Song
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.|Department of Medicine, Biomedical Engineering Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Artzi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D060833:Cellular Microenvironment; D004705:Endocytosis / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D009369:Neoplasms / Q000378:metabolism*; D009690:Nucleic Acid Conformation
chemical_list: D020100:Hydrogels; D035683:MicroRNAs