Researchers from the University of Palermo (Italy) generated targeted exosomes able to deliver Imatinib or BCR-ABL siRNA to CML cells in order to overcome pharmacological resistance. The benefit of using exosomes as a drug delivery system lies in the fact that they can be specifically targeted to a particular cell type by engineering exosome-producer cells. The researchers show that modified exosomes, containing IL3-Lamp2B, and loaded with Imatinib, are able to specifically target tumor cells in vivo, leading to a the reduction in tumor size. Furthermore, they found that modified exosomes are able to deliver functional BCR-ABL siRNA towards Imatinib-resistant CML cells.
Schematic representation of IL3-R-targeted exosomes
(A) HEK293T cells were transfected with a plasmid containing the recombinant human protein IL3-Lamp2b. Transfected cells were treated with Imatinib in order to generate Imatinib-containing IL3L exosomes or, transfected with BCR-ABL siRNA in order to generate siRNA-containing IL3L exosomes. The efficacy of engineered exosomes were tested in vitro and in vivo on Imatinib- sensitive or -resistant CML cells. (B) Schematic representation of Pinco plasmid construct containing IL3-Lamp2b.
Data reported are very promising and provide a rational base for the use of exosomes expressing a fragment of IL3 in a receptor-targeted therapy approach to treat CML patients and, in particular, in order to overcome pharmacological resistance.