Exosomal doxorubicin reduces the cardiac toxicity of doxorubicin

Giuseppe Toffoli; Mohamad Hadla; Giuseppe Corona; Isabella Caligiuri; Stefano Palazzolo; Sabrina Semeraro; Amelia Gamini; Vincenzo Canzonieri; Flavio Rizzolio

doi:10.2217/nnm.15.118

Exosomal doxorubicin reduces the cardiac toxicity of doxorubicin

Nanomedicine (Lond). 2015 Oct;10(19):2963-2971. doi: 10.2217/nnm.15.118. Epub 2015 Sep 30.

Authors

Affiliations

¹ Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
² Doctoral School in Pharmacological Sciences, University of Padua, Italy.
³ Doctoral School in Nanotechnology, University of Trieste, Italy.
⁴ Department of Chemical & Pharmaceutical Sciences, University of Trieste, Italy.

PMID: 26420143
DOI: 10.2217/nnm.15.118

Abstract

Aim: To test the efficacy and toxicity of exosomal doxorubicin (exoDOX) compared with free doxorubicin.

Materials & 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%.

Conclusion: We demonstrated that exoDOX was less toxic than DOX through its altered biodistribution.

Keywords: breast cancer; drug delivery; exosomal doxorubicin; exosome; nanomedicine; toxicity.