Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth.
Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth.
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DOI：
10.7150/thno.17092
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发表时间：
2017
期刊：
影响因子：
12.4
通讯作者：
Alessandro R
中科院分区：
文献类型：
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作者：
Bellavia D;Raimondo S;Calabrese G;Forte S;Cristaldi M;Patinella A;Memeo L;Manno M;Raccosta S;Diana P;Cirrincione G;Giavaresi G;Monteleone F;Fontana S;De Leo G;Alessandro R
尽管选择性Bcr-Abl抑制剂伊马替尼（Imatinib， IM）改善了慢性髓系白血病（CML）患者的预后，但仍遇到获得性耐药和长期不良反应。因此，迫切需要制定替代战略来克服耐药性。根据外泌体表面表达的分子，外泌体可以靶向特定的细胞。外泌体也可以装载各种分子，从而作为递送治疗剂的载体。在这项研究中，我们设计了HEK293T细胞来表达外泌体蛋白Lamp2b，与白细胞介素3 （IL3）片段融合。与正常造血细胞相比，il - 3受体（IL3- r）在CML母细胞中过度表达，因此能够作为癌症药物传递系统中的受体靶点。在这里，我们展示了装载伊马替尼或BCR-ABL siRNA的IL3L外泌体能够靶向CML细胞并抑制体外和体内癌细胞的生长。
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in vitro and in vivo cancer cell growth.