Interleukin 3-receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth

被引：345

作者：

Bellavia, Daniele ^{[1
]}

Raimondo, Stefania ^{[2
]}

Calabrese, Giovanna ^{[3
]}

Forte, Stefano ^{[3
]}

Cristaldi, Marta ^{[2
]}

Patinella, Agostina ^{[2
]}

Memeo, Lorenzo ^{[3
,4
]}

Manno, Mauro ^{[5
]}

Raccosta, Samuele ^{[5
]}

Diana, Patrizia ^{[6
]}

Cirrincione, Girolamo ^{[6
]}

Giavaresi, Gianluca ^{[1
,7
]}

Monteleone, Francesca ^{[2
]}

Fontana, Simona ^{[2
]}

De Leo, Giacomo ^{[2
]}

Alessandro, Riccardo ^{[2
]}

机构：

[1] Rizzoli Orthoped Inst, Innovat Technol Platform Tissue Engn Theranost &, I-90133 Palermo, Italy

[2] Univ Palermo, Dipartimento Biopatol & Biotecnol Med, I-90133 Palermo, Italy

[3] IOM Ric, Catania, Italy

[4] Ist Oncol Mediterraneo, Dipartimento Oncol Sperimentale, Catania, Italy

[5] Natl Res Council Italy, Inst Biophys, Palermo, Italy

[6] Univ Palermo, Dipartimento Sci & Tecnol Biol Chim & Farmaceut, I-90123 Palermo, Italy

[7] Rizzoli Orthoped Inst, Lab Preclin & Surg Studies, I-40136 Bologna, Italy

来源：

THERANOSTICS | 2017年 / 7卷 / 05期

关键词：

Chronic Myeloid Leukemia; Engineered exosomes; Drug delivery; Drug resistance; Interleukin; 3; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; DRUG-DELIVERY VEHICLES; CANCER-CELLS; IMATINIB MESYLATE; SIRNA DELIVERY; STEM-CELLS; THERAPY; THERAPEUTICS; RECEPTOR;

D O I：

10.7150/thno.17092

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页码：1333 / 1345

页数：13

共 44 条

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Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes [J].