Abstract 2205: Exosomal encapsulation of doxorubicin reduces the cardiac toxicity of mice
Exosomes are nanovesicles produced by cells embedded of cellular information and represent a formidable natural cargo for communication. The name "FedExosomes" denotes the general idea that exosomes could deliver cargo that conveniently manipulated could be of help for patient therapy. Up to now, a few papers demonstrated that modified exosomes could deliver drugs specifically to cancer cells and many laboratories are now studying their properties and compositions. Differently from previously published papers that focused on the efficacy of the doxorubicin encapsulated in exosomes (exoDOX) for the first time, we demonstrated that unmodified exosomes loaded with DOX are less toxic than free DOX by altering the biodistribution of the drug. The heart tissue of mice treated with a toxic dosage of DOX exhibited scattered cytoplasmic paranuclear vacuoles and focal intense eosinophilic cytoplasm, devoid of their transversal striations with moderate disarrangement of cardiomyocytes. The heart tissue of exoDOX treated mice at the same dosage appeared normal. Mass spectrometry studies confirmed that although the quantity of exoDOX in the blood was the same compared to DOX, accumulation in the heart was reduced of about forty percent. Maximum tolerated dose of exoDOX treated mice is double than free DOX. Mice treated at double concentration of exoDOX vs DOX have reduced tumor burden compared to free DOX without observable toxicity. We demonstrated that exoDOX increased the therapeutic index of DOX by reducing toxic side effects and envisage a similar mechanism for others chemotherapeutic drugs. Since the exosomes could be prepared directly from the patients, our preclinical approach could have a possible immediately application in the clinic. Citation Format: Flavio Rizzolio, Mohamad Hadla, Giuseppe Corona, Isabella Caligiuri, Stefano Palazzolo, Sabrina Semeraro, Amelia Gamini, Vincenzo Canzonieri, Giuseppe Toffoli. Exosomal encapsulation of doxorubicin reduces the cardiac toxicity of mice. [abstract] In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16 20; New Orleans, LA. Philadelphia (PA) AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2205.