Marín Gustavo H, Mansilla Eduardo, Mezzaroba Nelly, Zorzet Sonia, Núñez Luis, Larsen Gustavo, Tau José M, Maceira Alberto, Spretz Ruben, Mertz Carol, Ingrao Sabrina, Tripodo Claudio, Tedesco Francesco, Macor Paolo
CUCAIBA, Ministry of Health, Province of Buenos Aires, Calle 60 y 120, 1900-La Plata, Buenos Aires, Argentina.
Curr Clin Pharmacol. 2010 Nov;5(4):246-50. doi: 10.2174/157488410793352058.
The aim of this study was to determine if Rituximab coated Biodegradable Nanoparticles (BNPs) loaded with Chlorambucil and Hydroxychloroquine could induce apoptosis of B-Chronic Lymphocytic Leukemia (B-CLL), MEC-1 and BJAB cells in vitro and evaluate their toxic and therapeutic effects on a Human/Mouse Model of Burkitt Lymphoma at an exploratory, proof of concept scale. We found that Rituximab-Chlorambucil-Hydroxychloroquine BNPs induce a decrease in cell viability of malignant B cells in a dose-dependent manner. The mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the B-CLL cells after Annexin V/propidium iodide staining. Additional data revealed that these BNPs were non toxic for healthy animals, and had prolonged survival in this mice model of human lymphoma.
本研究的目的是确定负载苯丁酸氮芥和羟氯喹的利妥昔单抗包被的可生物降解纳米颗粒（BNP）是否能在体外诱导B细胞慢性淋巴细胞白血病（B-CLL）、MEC-1和BJAB细胞凋亡，并在探索性概念验证规模上评估它们对伯基特淋巴瘤人/小鼠模型的毒性和治疗效果。我们发现利妥昔单抗-苯丁酸氮芥-羟氯喹BNP以剂量依赖性方式诱导恶性B细胞的细胞活力下降。介导的细胞毒性是由凋亡引起的，并通过膜联蛋白V/碘化丙啶染色后监测B-CLL细胞得到证实。其他数据显示，这些BNP对健康动物无毒，并且在该人淋巴瘤小鼠模型中具有延长生存期的作用。
