TY - JOUR
T1 - Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth
AU - Bellavia, Daniele
AU - Raimondo, Stefania
AU - Calabrese, Giovanna
AU - Forte, Stefano
AU - Cristaldi, Marta
AU - Patinella, Agostina
AU - Memeo, Lorenzo
AU - Manno, Mauro
AU - Raccosta, Samuele
AU - Diana, Patrizia
AU - Cirrincione, Girolamo
AU - Giavaresi, Gianluca
AU - Monteleone, Francesca
AU - Fontana, Simona
AU - De Leo, Giacomo
AU - Alessandro, Riccardo
PY - 2017/3/16
Y1 - 2017/3/16
N2 - 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.
AB - 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.
KW - Chronic myeloid leukemia
KW - Drug delivery
KW - Drug resistance
KW - Engineered exosomes
KW - Interleukin 3
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U2 - 10.7150/thno.17092
DO - 10.7150/thno.17092
M3 - Article
AN - SCOPUS:85016711574
VL - 7
SP - 1333
EP - 1345
JO - Theranostics
JF - Theranostics
SN - 1838-7640
IS - 5
ER -