Neuroblastoma-targeted nanoparticles entrapping siRNA specifically knockdown ALK

Daniela Di Paolo, Chiara Brignole, Fabio Pastorino, Roberta Carosio, Alessia Zorzoli, Marzia Rossi, Monica Loi, Gabriella Pagnan, Laura Emionite, Michele Cilli, Silvia Bruno, Roberto Chiarle, Theresa M. Allen, Mirco Ponzoni, Patrizia Perri

Research output: Contribution to journalArticlepeer-review


RNA interference molecules have some advantages as cancer therapeutics, including a proved efficacy on both wild-type (WT) and mutated transcripts and an extremely high sequence-specificity. The most significant hurdle to be overcome if exogenous small interfering RNAs (siRNA) is to be used therapeutically is the specific, effective, nontoxic delivery of siRNA to its intracellular site of action. At present, human applications are confined almost exclusively to targets within the liver, where the delivery systems naturally accumulate, and extra-hepatic targets remain a challenge. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has recently been shown to contribute to the cell growth and progression of human neuroblastoma (NB). We investigated its potential as a therapeutic target in NB by generating anti-GD 2-targeted nanoparticles that carry ALK-directed siRNA, which are specifically and efficiently delivered to GD 2-expressing NB cells. Relative to free ALK-siRNA, anti-GD 2-targeted liposomal formulations of ALK-siRNA had low plasma clearance, increased siRNA stability, and improved binding, uptake, silencing and induction of cell death, and specificity for NB cells. In NB xenografts, intravenous (i.v.) injection of the targeted ALK-siRNA liposomes showed gene-specific antitumor activity with no side effects. ALK-selective siRNA entrapped in anti-GD 2-targeted nanoparticles is a promising new modality for NB treatment.

Original languageEnglish
Pages (from-to)1131-1140
Number of pages10
JournalMolecular Therapy
Issue number6
Publication statusPublished - Jun 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology


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