Exosomes as an siRNA delivery vehicle

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

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.

Bellavia D, Raimondo S, Calabrese G, Forte S, Cristaldi M, Patinella A, Memeo L, Manno M, Raccosta S, Diana P, Cirrincione G, Giavaresi G, Monteleone F, Fontana S, De Leo G, Alessandro R. (2017) Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth. Theranostics 7(5):1333-1345. [article]

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