@article{6e634c8ab9964725a3f425850ffbfc88,
title = "A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles",
abstract = "Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term sideeffects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant cells. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanoparticles coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated/deleted leukemia cells expressing a low amount of CD20, but also circulating primary cells isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders. [Figure not available: see fulltext.]",
keywords = "chronic lymphocytic leukemia, immune targeted nanoparticles, treatment, xenograft model",
author = "Sara Capolla and Nelly Mezzaroba and Sonia Zorzet and Claudio Tripodo and Ramiro Mendoza-Maldonado and Marilena Granzotto and Francesca Vita and Ruben Spretz and Gustavo Larsen and Sandra Noriega and Eduardo Mansilla and {Dal Bo}, Michele and Valter Gattei and Gabriele Pozzato and Luis N{\'u}{\~n}ez and Paolo Macor",
note = "Funding Information: This study has been made possible by research grants from Italian Association for Cancer Research (AIRC Project No. 12965/2012), Italian Ministry of Health (Nos. GR-2011-02346826 and GR-2011-02347441), Fondazione Casali - Trieste, Italy and Stiftung Foundation - Liechtenstein. Nanoparticles fabrication at LNK Chemsolutions, USA, was possible in part by Grant 2R44CA135906-02 (SBIR Phase II) from the National Institutes of Health (USA) to Ruben Spretz, Gustavo Larsen, Sandra Noriega and Luis N??ez. Conflict-of-interest disclosure: Ruben Spretz, Gustavo Larsen, Sandra Noriega and Luis N??ez working in Biotarget Inc. and LNK Chemsolutions LLC have commercial interests in the particle systems described in this work. No conflicts of interest for the other authors. Funding Information: This study has been made possible by research grants from Italian Association for Cancer Research (AIRC Project No. 12965/2012), Italian Ministry of Health (Nos. GR-2011-02346826 and GR-2011-02347441), Fondazione Casali - Trieste, Italy and Stiftung Foundation - Liechtenstein. Nanoparticles fabrication at LNK Chemsolutions, USA, was possible in part by Grant 2R44CA135906-02 (SBIR Phase II) from the National Institutes of Health (USA) to Ruben Spretz, Gustavo Larsen, Sandra Noriega and Luis N{\'u}{\~n}ez. Conflict-of-interest disclosure: Ruben Spretz, Gustavo Larsen, Sandra Noriega and Luis N{\'u}{\~n}ez working in Biotarget Inc. and LNK Chemsolutions LLC have commercial interests in the particle systems described in this work. No conflicts of interest for the other authors. Publisher Copyright: {\textcopyright} 2015, Tsinghua University Press and Springer-Verlag Berlin Heidelberg.",
year = "2016",
month = feb,
day = "1",
doi = "10.1007/s12274-015-0935-3",
language = "English (US)",
volume = "9",
pages = "537--548",
journal = "Nano Research",
issn = "1998-0124",
publisher = "Press of Tsinghua University",
number = "2",
}