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- W2023795307 abstract "Background Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD2), providing a target for tumor-specific delivery. Principal Findings Nanoparticles encapsulating miR-34a and conjugated to a GD2 antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors. Significance These novel findings highlight the potential of anti-GD2-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD2-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth." @default.
- W2023795307 created "2016-06-24" @default.
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- W2023795307 date "2012-05-25" @default.
- W2023795307 modified "2023-10-18" @default.
- W2023795307 title "Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated Nanoparticles" @default.
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- W2023795307 doi "https://doi.org/10.1371/journal.pone.0038129" @default.
- W2023795307 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3360657" @default.
- W2023795307 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22662276" @default.
- W2023795307 hasPublicationYear "2012" @default.
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