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

被引:17
|
作者
Capolla, Sara [1 ]
Mezzaroba, Nelly [1 ]
Zorzet, Sonia [1 ]
Tripodo, Claudio [2 ]
Mendoza-Maldonado, Ramiro [3 ]
Granzotto, Marilena [4 ]
Vita, Francesca [1 ]
Spretz, Ruben [5 ]
Larsen, Gustavo [5 ,6 ]
Noriega, Sandra [5 ]
Mansilla, Eduardo [7 ]
Dal Bo, Michele [8 ]
Gattei, Valter [8 ]
Pozzato, Gabriele [4 ]
Nunez, Luis [5 ,6 ]
Macor, Paolo [1 ,9 ]
机构
[1] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy
[2] Univ Palermo, Dept Human Pathol, I-90133 Sicily, Italy
[3] Natl Lab Consorzio Interuniv Biotecnol CIB, Mol Oncol Unit, I-34012 Trieste, Italy
[4] Univ Trieste, Dipartimento Univ Clin Sci Med Chirurg & Salute, I-34149 Trieste, Italy
[5] LNK Chemsolut LLC, Lincoln, NE 68521 USA
[6] Biotarget Inc, Chicago, IL 60637 USA
[7] Minist Hlth, Ctr Unico Coordinador Ablac & Implante Prov Bueno, La Plata, Buenos Aires, Argentina
[8] IRCCS, Ctr Riferimento Oncol, Clin & Expt Oncohematol Unit, I-33081 Aviano, Italy
[9] Callerio Fdn Onlus, Inst Biol Res, I-34127 Trieste, Italy
基金
美国国家卫生研究院;
关键词
chronic lymphocytic leukemia; immune targeted nanoparticles; treatment; xenograft model; CHRONIC LYMPHOCYTIC-LEUKEMIA; HYDROXYCHLOROQUINE; DIAGNOSIS; CELLS; XENOGRAFT; SURVIVAL; CYCLOPHOSPHAMIDE; BIODISTRIBUTION; STRATEGIES; RESISTANCE;
D O I
10.1007/s12274-015-0935-3
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
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 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.
引用
收藏
页码:537 / 548
页数:12
相关论文
共 50 条
  • [1] A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles
    Sara Capolla
    Nelly Mezzaroba
    Sonia Zorzet
    Claudio Tripodo
    Ramiro Mendoza-Maldonado
    Marilena Granzotto
    Francesca Vita
    Ruben Spretz
    Gustavo Larsen
    Sandra Noriega
    Eduardo Mansilla
    Michele Dal Bo
    Valter Gattei
    Gabriele Pozzato
    Luis Núñez
    Paolo Macor
    [J]. Nano Research, 2016, 9 : 537 - 548
  • [2] New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine- Loaded Anti-CD20 Nanoparticles
    Mezzaroba, Nelly
    Zorzet, Sonia
    Secco, Erika
    Biffi, Stefania
    Tripodo, Claudio
    Calvaruso, Marco
    Mendoza-Maldonado, Ramiro
    Capolla, Sara
    Granzotto, Marilena
    Spretz, Ruben
    Larsen, Gustavo
    Noriega, Sandra
    Lucafo, Marianna
    Mansilla, Eduardo
    Garrovo, Chiara
    Marin, Gustavo H.
    Baj, Gabriele
    Gattei, Valter
    Pozzato, Gabriele
    Nunez, Luis
    Macor, Paolo
    [J]. PLOS ONE, 2013, 8 (09):
  • [3] New Therapeutic Approach for the Treatment of B-Cell Disorders Using Chlorambucil/Hydroxychloroquine-Loaded AntiCD20 Nanoparticles
    Pozzato, Gabriele
    Mezzaroba, Nelly
    Zorzet, Sonia
    Secco, Erika
    Biffi, Stefania
    Tripodo, Claudio
    Calvaruso, Marco
    Nunez, Luis
    Spretz, Rubens
    Larsen, Gustavo
    Noriega, Sandra
    Garrovo, Chiara
    Marin, Gustavo
    Mansilla, Edoardo
    Macor, Paolo
    [J]. BLOOD, 2012, 120 (21)
  • [4] Is there a role for anti-CD20 antibodies in CLL?
    Shah, Harsh R.
    Stephens, Deborah M.
    [J]. HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM, 2021, (01) : 68 - 75
  • [5] Treatment of chronic lymphocytic leukemia (CLL)with the anti-CD20 antibody rituximab.
    Emmerich, B
    Huhn, D
    Peschel, C
    Wilhelm, M
    von Schilling, C
    Bentz, M
    Hallek, M
    Knauf, B
    Kuse, R
    Ho, AD
    [J]. BLOOD, 1999, 94 (10) : 309B - 309B
  • [6] Real-life retrospective comparison of chlorambucil plus anti-CD20 antibody versus ibrutinib alone as frontline treatment for unfit CLL/SLL
    Loscertales, Javier
    Delgado, Julio
    Carla Oliveira, Ana
    Martin Rodriguez, Lucia
    Ferra Coll, Christelle
    Ramirez-Payer, Angel
    Hernandez, Jose-Angel
    Vidal Mancenido, Maria-Jesus
    Prat, Ana Muntanola
    Garcia, Abelardo Barez
    Perez, Maria Angeles Medina
    Rubio-Martinez, Araceli
    Collado, Rosa
    Carmen Mas-Ochoa, Mari
    Mascaro Riera, Martin
    Navarro, Almudena
    Romero Fernandez, Pilar
    Sanz-Garcia, Ancor
    Bosch, Francesc
    [J]. LEUKEMIA & LYMPHOMA, 2020, 61 : 128 - 130
  • [7] Should Venetoclax Be Used With or Without Anti-CD20 Therapy for CLL?
    Furman, Richard R.
    [J]. CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY, 2021, 19 (04) : 209 - 211
  • [8] BTK inhibitors and anti-CD20 monoclonal antibodies for treatment-naive elderly patients with CLL
    Rogers, Andrew
    Woyach, Jennifer A.
    [J]. THERAPEUTIC ADVANCES IN HEMATOLOGY, 2020, 11
  • [9] Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy
    Briani, C.
    Visentin, A.
    Salvalaggio, A.
    Cacciavillani, M.
    Trentin, L.
    [J]. EUROPEAN JOURNAL OF NEUROLOGY, 2019, 26 (02) : 371 - 375
  • [10] Anti-CD20 (rituximab) treatment for atopic eczema
    Sediva, Anna
    Kayserova, Jana
    Vernerova, Eva
    Polouckova, Andrea
    Capkova, Stepanka
    Spisek, Radek
    Bartunkova, Jirina
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 121 (06) : 1515 - 1516