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Exosomal doxorubicin reduces the cardiac toxicity of doxorubicin. 2015

Giuseppe Toffoli, and Mohamad Hadla, and Giuseppe Corona, and Isabella Caligiuri, and Stefano Palazzolo, and Sabrina Semeraro, and Amelia Gamini, and Vincenzo Canzonieri, and Flavio Rizzolio
Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.

OBJECTIVE To test the efficacy and toxicity of exosomal doxorubicin (exoDOX) compared with free doxorubicin. METHODS The cytotoxic effects of exoDOX were tested in vitro and in nude mice by measuring the tumor volume. The toxic effects were evaluated by measuring the bodyweight and through histopathologic analyses. The biodistribution of DOX was assessed by MS. RESULTS In vitro and in vivo studies showed that exosomes did not decrease the efficacy of DOX. Surprisingly, exoDOX showed no cardiotoxicity as observed in DOX-treated mice and MS studies confirmed that the accumulation of exoDOX in the heart was reduced by approximately 40%. CONCLUSIONS We demonstrated that exoDOX was less toxic than DOX through its altered biodistribution.

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