title: Layered gadolinium-based nanoparticle as a novel delivery platform for microRNA therapeutics.
abstract: Specific expression patterns of microRNA (miRNA) molecules have been linked to cancer initiation, progression, and metastasis. The accumulating evidence for the role of oncogenic or tumor-suppressing miRNAs identified the need for nano-scaled platform that can help deliver nucleotides to modulate miRNAs. Here we report the synthesis of novel layered gadolinium hydroxychloride (LGdH) nanoparticles, a member of the layered double hydroxide (LDH) family, with physiochemical properties suitable for cell uptake and tracing via magnetic resonance (MR) imaging. As a proof of concept, we demonstrate the inhibition of mature miRNA-10b in metastatic breast cancer cell line using LGdH nanoparticle as a delivery platform. Through characterization analysis, we show that nanoparticles are easily and stably loaded with anti-miRNA oligonucleotides (AMO) and efficiently penetrate cell membranes. We demonstrate that AMOs delivered by LGdH nanoparticles remain functional by inducing changes in the expression of its downstream effector and by curbing the invasive properties. Furthermore, we demonstrate the traceability of LGdH nanoparticles via T1 weighted MR imaging. LGdH nanoparticles, which are biocompatible with cells in vitro, provide a promising multifunctional platform for microRNA therapeutics through their diagnostic, imaging, and therapeutic potentials.
authors.affiliation: Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Yoo
authors.forename: Rene
authors.initials: R
authors.lastname: Razzak
authors.forename: Eric
authors.initials: E
authors.lastname: Bédard
authors.forename: Linghong
authors.initials: L
authors.lastname: Guo
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Shaw
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moore
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D005682:Gadolinium / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D035683:MicroRNAs / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D001672:Biocompatible Materials; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D005682:Gadolinium