title: B-cell receptor-guided delivery of peptide-siRNA complex for B-cell lymphoma therapy.
abstract: BACKGROUND
  Despite the clinical response of conventional anticancer therapy, including chemotherapeutic treatments, radiation therapy and corticosteroids, tumorigenic B-cell lymphomas show an incomplete response to clinical practices that result in a minimal residual disease (MRD) where few residual neoplastic cells undetected in vivo, replenish the cancer cell reservoir. This scenario, which is also shared with other cancer diseases, requires the development of strategies to advance in novel, selective targeting toward the tumorigenic cells that survive to the anticancer agents.
  
  
  METHODS
  Here, we have taken advantage of the therapeutic properties of an idiotype specific peptide (pA20-36) that bind specifically to murine B-lymphoma cells in the setting of an anti cancer strategy, based on the selected delivery of electrostatic-based complex, peptide-siRNA. To this end, two engineered, arginine rich, peptides that included the pA20-36 targeting sequence were designed to bind fluorescent-labelled siRNA. One peptide presented 9 Arg at the C-terminal of pA20-36 whereas the other included 5 Arg at the N- and C-terminus, respectively.
  
  
  RESULTS
  Compared to the control and random peptide-siRNA complexes, both pA20-36-siRNA complexes were endowed with the selective delivering of fluorescent-labelled siRNA toward the A20 murine B-cell lymphoma, as evaluated by cytofluorimetry and confocal microscopy, whereas fluorescent-labelled siRNA alone was not internalized in the selected cells. Compared to peptide controls, the use of the modified pA20-36 peptides complexed with siRNA anti-GAPDH and anti-Bcl2 showed a down-regulation in the expression levels of the corresponding genes.
  
  
  CONCLUSIONS
  Peptide-siRNA complex can be suitable tool for both selective peptide-driven cell targeting and gene silencing. In this setting, the improvement of this strategy is expected to provide a safe and non-invasive approach for the delivery of therapeutic molecules.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, I-80131 Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Migliaccio
authors.affiliation: Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, I-88100 Germaneto, Catanzaro, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Palmieri
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, I-80131 Naples, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Ruggiero
authors.affiliation: Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, I-88100 Germaneto, Catanzaro, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fiume
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, I-80131 Naples, Italy.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Martucci
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, I-80131 Naples, Italy.
authors.forename: Iris
authors.initials: I
authors.lastname: Scala
authors.affiliation: Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, I-88100 Germaneto, Catanzaro, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Quinto
authors.affiliation: Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, I-88100 Germaneto, Catanzaro, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scala
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, I-80131 Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lamberti
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, I-80131 Naples, Italy ; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini, I-80131 Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Arcari
keywords: B lymphoma cells; Id-peptide; Minimal residual disease (MRD); Peptide engineering; Peptide-siRNA complex