期刊
THERANOSTICS
卷 7, 期 5, 页码 1333-1345出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.17092
关键词
Chronic Myeloid Leukemia; Engineered exosomes; Drug delivery; Drug resistance; Interleukin 3
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- University of Palermo
- Fondazione Veronesi
- FIRC (Fondazione Italiana Ricerca sul Cancro)
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.
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