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Nanoparticle-based strategy for personalized B-cell lymphoma therapy

Authors Martucci NM, Migliaccio N, Ruggiero I, Albano F, Calì G, Romano S, Terracciano M, Rea I, Arcari P, Lamberti A

Received 1 August 2016

Accepted for publication 29 September 2016

Published 16 November 2016 Volume 2016:11 Pages 6089—6101


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster

Nicola M Martucci,1,* Nunzia Migliaccio,1,* Immacolata Ruggiero,1,* Francesco Albano,2 Gaetano Calì,3 Simona Romano,1 Monica Terracciano,4 Ilaria Rea,4 Paolo Arcari,1 Annalisa Lamberti1

1Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, 2Department of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, Catanzaro, 3Institute of Endocrinology and Molecular Oncology, 4Institute for Microelectronics and Microsystems, National Research Council, Naples, Italy

*These authors contributed equally to this work

Abstract: B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas.

Keywords: diatomite, active targeting, Bcl2, small interfering RNA, personalized therapy

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