New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles
| Autor: | Chiara Garrovo, Gustavo Horacio Marín, Marilena Granzotto, Gabriele Baj, Sonia Zorzet, Luis Nunez, Stefania Biffi, Nelly Mezzaroba, Ruben Spretz, Sandra Noriega, Marianna Lucafò, Eduardo Mansilla, Erika Secco, Gustavo Larsen, Valter Gattei, Marco Calvaruso, Ramiro Mendoza-Maldonado, Sara Capolla, Gabriele Pozzato, Claudio Tripodo, Paolo Macor |
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| Přispěvatelé: | 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, GH, Baj, G, Gattei, V, Pozzato, G, Núñez, L, Macor, P., Mezzaroba, Nelly, Zorzet, Sonia, Mendoza Maldonado, R, Capolla, Sara, Lucafo, Marianna, Marín, Gh, Baj, Gabriele, Pozzato, Gabriele, Macor, Paolo |
| Rok vydání: | 2013 |
| Předmět: |
Lymphoma
medicine.medical_treatment lcsh:Medicine Apoptosis nanoparticles Targeting strategies Aggressive lymphoma Mice SCID Pharmacology Antibodies Monoclonal Murine-Derived Mice Drug Delivery Systems 0302 clinical medicine immune system diseases hemic and lymphatic diseases NANOPARTICLES Medicine lcsh:Science CD20 0303 health sciences Multidisciplinary biology ANTI-CD20 B-CELL MALIGNANCIES nanoparticle Flow Cytometry Immunohistochemistry 3. Good health Drug Combinations Leukemia 030220 oncology & carcinogenesis Monoclonal Targeting strategie Female Rituximab Hydroxychloroquine Research Article medicine.drug Lymphoma B-Cell Cell Survival 03 medical and health sciences Microscopy Electron Transmission Autophagy Animals 030304 developmental biology Chlorambucil business.industry lcsh:R Immunotherapy Antigens CD20 medicine.disease Disease Models Animal biology.protein lcsh:Q business |
| Zdroj: | PLoS ONE, Vol 8, Iss 9, p e74216 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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