Nanoparticle-based strategy for personalized B-cell lymphoma therapy
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. Speci...
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pubmed-51179542016-11-28 Nanoparticle-based strategy for personalized B-cell lymphoma therapy Martucci, Nicola M Migliaccio, Nunzia Ruggiero, Immacolata Albano, Francesco Calì, Gaetano Romano, Simona Terracciano, Monica Rea, Ilaria Arcari, Paolo Lamberti, Annalisa Original Research 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. Dove Medical Press 2016-11-16 /pmc/articles/PMC5117954/ /pubmed/27895482 http://dx.doi.org/10.2147/IJN.S118661 Text en © 2016 Martucci et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
repository_type |
Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
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NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
Martucci, Nicola M Migliaccio, Nunzia Ruggiero, Immacolata Albano, Francesco Calì, Gaetano Romano, Simona Terracciano, Monica Rea, Ilaria Arcari, Paolo Lamberti, Annalisa |
spellingShingle |
Martucci, Nicola M Migliaccio, Nunzia Ruggiero, Immacolata Albano, Francesco Calì, Gaetano Romano, Simona Terracciano, Monica Rea, Ilaria Arcari, Paolo Lamberti, Annalisa Nanoparticle-based strategy for personalized B-cell lymphoma therapy |
author_facet |
Martucci, Nicola M Migliaccio, Nunzia Ruggiero, Immacolata Albano, Francesco Calì, Gaetano Romano, Simona Terracciano, Monica Rea, Ilaria Arcari, Paolo Lamberti, Annalisa |
author_sort |
Martucci, Nicola M |
title |
Nanoparticle-based strategy for personalized B-cell lymphoma therapy |
title_short |
Nanoparticle-based strategy for personalized B-cell lymphoma therapy |
title_full |
Nanoparticle-based strategy for personalized B-cell lymphoma therapy |
title_fullStr |
Nanoparticle-based strategy for personalized B-cell lymphoma therapy |
title_full_unstemmed |
Nanoparticle-based strategy for personalized B-cell lymphoma therapy |
title_sort |
nanoparticle-based strategy for personalized b-cell lymphoma therapy |
description |
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. |
publisher |
Dove Medical Press |
publishDate |
2016 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117954/ |
_version_ |
1613735724996100096 |