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RESEARCH PRODUCT
A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles
Claudio TripodoMarilena GranzottoSara CapollaGabriele PozzatoRuben SpretzMichele Dal BoLuis NunezSonia ZorzetPaolo MacorGustavo LarsenSandra NoriegaNelly MezzarobaEduardo MansillaFrancesca VitaRamiro Mendoza-maldonadoValter Gatteisubject
0301 basic medicineChronic lymphocytic leukemiaxenograft modelchronic lymphocytic leukemia; immune targeted nanoparticles; treatment; xenograft model; Electrical and Electronic Engineering; Materials Science (all)Nanotechnology03 medical and health sciencesTherapeutic approach0302 clinical medicinehemic and lymphatic diseasesmedicineGeneral Materials ScienceElectrical and Electronic EngineeringCytotoxicityCD20immune targeted nanoparticletreatmentChlorambucilbiologybusiness.industryTherapeutic effectHydroxychloroquineCondensed Matter Physicsmedicine.diseaseAtomic and Molecular Physics and OpticsLeukemia030104 developmental biology030220 oncology & carcinogenesisimmune targeted nanoparticlesCancer researchbiology.proteinchronic lymphocytic leukemiaMaterials Science (all)businessmedicine.drugdescription
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.]
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 | Nano Research |