Theranostics 2017; 7(5):1333-1345. doi:10.7150/thno.17092

Research Paper

Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth

Daniele Bellavia1*, Stefania Raimondo2*, Giovanna Calabrese3, Stefano Forte3, Marta Cristaldi2, Agostina Patinella2, Lorenzo Memeo3, 4, Mauro Manno5, Samuele Raccosta5, Patrizia Diana6, Girolamo Cirrincione6, Gianluca Giavaresi1,7, Francesca Monteleone2, Simona Fontana2, Giacomo De Leo2, Riccardo Alessandro2✉

1. Rizzoli Orthopedic Institute, Innovative Technological Platform for Tissue Engineering, Theranostics and Oncology, Palermo 90133, Italy;
2. Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo 90133, Italy;
3. IOM Ricerca, Viagrande, Catania, Italy;
4. Dipartimento di Oncologia Sperimentale, Istituto Oncologico del Mediterraneo, Viagrande, Catania, Italy;
5. National Research Council of Italy, Institute of Biophysics, Palermo, Italy;
6. Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, University of Palermo, Palermo 90123, Italy;
7. Rizzoli Orthopedic Institute, Laboratory of Preclinical and Surgical Studies, Bologna 40136, Italy.
* These authors contributed equally to this work

Abstract

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.

Keywords: Chronic Myeloid Leukemia, Engineered exosomes, Drug delivery, Drug resistance, Interleukin 3.

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How to cite this article:
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. Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth. Theranostics 2017; 7(5):1333-1345. doi:10.7150/thno.17092. Available from http://www.thno.org/v07p1333.htm