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RESEARCH PRODUCT
Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth
Francesca MonteleoneRiccardo AlessandroGirolamo CirrincioneStefania RaimondoGiacomo De LeoSimona FontanaDaniele BellaviaSamuele RaccostaStefano ForteGianluca GiavaresiMarta CristaldiMauro MannoLorenzo MemeoAgostina PatinellaPatrizia DianaGiovanna Calabresesubject
0301 basic medicineMedicine (miscellaneous)PharmacologyEngineered exosomeExosomesInterleukin 3Antineoplastic AgentMiceHEK293 Cellhemic and lymphatic diseasesDrug CarrierPharmacology Toxicology and Pharmaceutics (miscellaneous)Drug CarriersChronic myeloid leukemiaMyeloid leukemiaChronic myeloid leukemia; Drug delivery; Drug resistance; Engineered exosomes; Interleukin 3; Animals; Antineoplastic Agents; Cell Line Tumor; Cell Proliferation; Disease Models Animal; Drug Carriers; Exosomes; HEK293 Cells; Heterografts; Humans; Imatinib Mesylate; Leukemia Myelogenous Chronic BCR-ABL Positive; Mice; Receptors Interleukin-3; Treatment Outcome3. Good healthTreatment OutcomeImatinib MesylateHeterograftsHeterograftResearch Papermedicine.drugHumanEngineered exosomesAntineoplastic Agents03 medical and health sciencesIn vivoCell Line TumorLeukemia Myelogenous Chronic BCR-ABL PositivemedicineAnimalsHumansneoplasmsInterleukin 3.Interleukin 3Cell Proliferationbusiness.industryAnimalImatinibmedicine.diseaseMicrovesiclesReceptors Interleukin-3ExosomeDisease Models AnimalHEK293 Cells030104 developmental biologyImatinib mesylateDrug resistanceCancer cellDrug deliverybusinessChronic myelogenous leukemiadescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-03-01 |