Type

Journal Article

Authors

Raymond L Stallings
Andrew M Davidoff
Holger N Lode
Catherine Y Ng
Olga Piskareva
Isabella M Bray
Raquel Domingo-Fernandez
Harry Harvey
Suzanne Prenter
Colette McDonagh
and 5 others

Subjects

Biochemistry

Topics
micrornas neuroblastoma chemistry immunology genetics metabolism drug therapy neovascularization pathologic oncogene proteins mycn protein human cell line tumor ganglioside gd2 animals mirn34 microrna human apoptosis mice scid administration dosage xenograft model antitumor assays gene expression profiling mice nuclear proteins drug effects humans gene expression nanoconjugates gangliosides

Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. (2012)

Abstract 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 (GD(2)), providing a target for tumor-specific delivery. Nanoparticles encapsulating miR-34a and conjugated to a GD(2) 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. These novel findings highlight the potential of anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD(2)-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Raymond L Stallings, Andrew M Davidoff, Holger N Lode, Catherine Y Ng, Olga Piskareva, Isabella M Bray, Raquel Domingo-Fernandez, Harry Harvey, Suzanne Prenter, Colette McDonagh and 5 others

Experts in our system

1
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
2
Olga Piskareva
Royal College of Surgeons in Ireland
Total Publications: 12
 
3
Isabella Bray
Royal College of Surgeons in Ireland
Total Publications: 35
 
4
Harry Harvey
Royal College of Surgeons in Ireland
Total Publications: 11