New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles

Nelly Mezzaroba, Sonia Zorzet, Erika Secco, Stefania Biffi, Claudio Tripodo, Marco Calvaruso, Ramiro Mendoza-Maldonado, Sara Capolla, Marilena Granzotto, Ruben Spretz, Gustavo Larsen, Sandra Noriega, Marianna Lucafò, Eduardo Mansilla, Chiara Garrovo, Gustavo H. Marín, Gabriele Baj, Valter Gattei, Gabriele Pozzato, Luis NúñezPaolo Macor

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23 Scopus citations

Abstract

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

Original languageEnglish (US)
Article numbere74216
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 30 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Mezzaroba, N., Zorzet, S., Secco, E., Biffi, S., Tripodo, C., Calvaruso, M., Mendoza-Maldonado, R., Capolla, S., Granzotto, M., Spretz, R., Larsen, G., Noriega, S., Lucafò, M., Mansilla, E., Garrovo, C., Marín, G. H., Baj, G., Gattei, V., Pozzato, G., ... Macor, P. (2013). New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles. PloS one, 8(9), [e74216]. https://doi.org/10.1371/journal.pone.0074216