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Title of Journal: Nano Res

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Abbravation: Nano Research

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Tsinghua University Press

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DOI

10.1007/s00339-011-6381-5

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1998-0000

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A new approach for the treatment of CLL using chlo

Authors: Sara Capolla Nelly Mezzaroba Sonia Zorzet Claudio Tripodo Ramiro MendozaMaldonado Marilena Granzotto Francesca Vita Ruben Spretz Gustavo Larsen Sandra Noriega Eduardo Mansilla Michele Dal Bo Valter Gattei Gabriele Pozzato Luis Núñez Paolo Macor
Publish Date: 2015/12/10
Volume: 9, Issue: 2, Pages: 537-548
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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 longterm sideeffects of therapeutics for all leukemia patients there is an urgent need for novel therapeutic strategies for difficulttotreat 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 nonmalignant 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 antiCD20 antibodyWe first demonstrated the ability of the nanoparticles to target and internalize in tumor Bcells Moreover these nanoparticles could kill not only p53mutated/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 antiCD20 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 Bcell disorders

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