New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.
New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.
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DOI：
10.1371/journal.pone.0074216
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Macor P
中科院分区：
文献类型：
--
作者：
Mezzaroba N;Zorzet S;Secco E;Biffi S;Tripodo C;Calvaruso M;Mendoza-Maldonado R;Capolla S;Granzotto M;Spretz R;Larsen G;Noriega S;Lucafò M;Mansilla E;Garrovo C;Marín GH;Baj G;Gattei V;Pozzato G;Núñez L;Macor P
目前的B细胞疾病治疗利用剂量密集的化疗方案和通过使用单克隆抗体的免疫疗法。不幸的是，它们可能导致治疗剂的肿瘤分布不足，并且经常对患者造成不良影响。在这篇文章中，我们提出了一种新的治疗方法，其中相对高剂量的羟氯喹和苯丁酸氮芥被加载到可生物降解的纳米颗粒与抗CD 20抗体包被。我们证明了它们有效靶向和内化肿瘤B细胞的能力。此外，这些纳米颗粒不仅能够杀死表达少量CD 20的p53突变/缺失的淋巴瘤细胞系，而且能够杀死从慢性淋巴细胞白血病患者纯化的循环原代细胞。它们的安全性在健康小鼠中得到了证实，它们在伯基特淋巴瘤的新模型中得到了治疗效果。后者是一种侵袭性淋巴增生性疾病的原型。体外和体内数据显示，与游离细胞毒性剂或利妥昔单抗相比，负载有羟氯喹和苯丁酸氮芥的抗CD 20纳米颗粒增加肿瘤细胞杀伤的能力。这些结果揭示了携带羟氯喹和苯丁酸氮芥的抗CD 20纳米颗粒用于控制侵袭性淋巴瘤的播散模型的潜力，并为采用这种治疗方法治疗B细胞疾病的想法提供了证据。
Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.
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影响因子：
20.3
作者：
Agemy, Lilach;Sugahara, Kazuki N.;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki
影响因子：
20.3
作者：
Bellosillo, B;Villamor, N;Montserrat, E
通讯作者：
Montserrat, E
影响因子：
14
作者：
Acharya, Sarbari;Dilnawaz, Fahima;Sahoo, Sanjeeb K.
通讯作者：
Sahoo, Sanjeeb K.
影响因子：
2.8
作者：
Biffi, Steania;Garrovo, Chiara;Lorusso, Vito
通讯作者：
Lorusso, Vito
DOI：
10.1158/1078-0432.ccr-10-2634
发表时间：
2011-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Amaravadi RK;Lippincott-Schwartz J;Yin XM;Weiss WA;Takebe N;Timmer W;DiPaola RS;Lotze MT;White E
通讯作者：
White E