A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Claudio Tripodo, Nelly Mezzaroba, Sara Capolla, Luis Núñez, Ramiro Mendoza-Maldonado, Paolo Macor, Sandra Noriega, Michele Dal Bo, Ruben Spretz, Marilena Granzotto, Francesca Vita, Sonia Zorzet, Valter Gattei, Gabriele Pozzato, Gustavo Larsen, Eduardo Mansilla

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.]
Original languageEnglish
Pages (from-to)537-548
Number of pages12
JournalNano Research
Volume9
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • General Materials Science
  • Electrical and Electronic Engineering

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