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

• Published in: Nano research Vol. 9; no. 2; pp. 537 - 548
• Main Authors: Capolla, Sara, Mezzaroba, Nelly, Zorzet, Sonia, Tripodo, Claudio, Mendoza-Maldonado, Ramiro, Granzotto, Marilena, Vita, Francesca, Spretz, Ruben, Larsen, Gustavo, Noriega, Sandra, Mansilla, Eduardo, Dal Bo, Michele, Gattei, Valter, Pozzato, Gabriele, Núñez, Luis, Macor, Paolo
• Format: Journal Article
• Language: English
• Published: Beijing Tsinghua University Press 01.02.2016; Springer Nature B.V
• Subjects: Atomic/Molecular Structure and Spectra; Biodegradability; Biodegradation; Biomedicine; Biotechnology; CD20 antigen; Chemical compounds; Chemistry and Materials Science; Chlorambucil; Chronic lymphocytic leukemia; Circulating; Condensed Matter Physics; Cytotoxicity; Disorders; Drug delivery systems; Drugs; Hydroxychloroquine; Leukemia; Leukemias; Lymphatic leukemia; Lymphocytes B; Materials Science; Medical prognosis; Mice; Nanoparticles; Nanostructure; Nanotechnology; p53 Protein; Patients; Pharmacology; Research Article; Toxicity; Viability; 丁酸; 加载; 氮芥; 氯喹; 治疗方案; 淋巴细胞性白血病; 淋巴细胞白血病; 聚合物纳米粒子; immune targeted nanoparticles; treatment; xenograft model; chronic lymphocytic leukemia
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-015-0935-3

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 side- effects 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 ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides 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 ceils 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.