Toffoli Giuseppe, Hadla Mohamad, Corona Giuseppe, Caligiuri Isabella, Palazzolo Stefano, Semeraro Sabrina, Gamini Amelia, Canzonieri Vincenzo, Rizzolio Flavio
Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
Doctoral School in Pharmacological Sciences, University of Padua, Italy.
Nanomedicine (Lond). 2015 Oct;10(19):2963-2971. doi: 10.2217/nnm.15.118. Epub 2015 Sep 30.
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.
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%.
We demonstrated that exoDOX was less toxic than DOX through its altered biodistribution.
测试外泌体阿霉素(exoDOX)与游离阿霉素相比的疗效和毒性。
通过测量肿瘤体积在体外和裸鼠体内测试exoDOX的细胞毒性作用。通过测量体重和组织病理学分析评估毒性作用。通过质谱法评估阿霉素的生物分布。
体外和体内研究表明,外泌体不会降低阿霉素的疗效。令人惊讶的是,exoDOX未显示出在阿霉素治疗的小鼠中观察到的心脏毒性,质谱研究证实exoDOX在心脏中的积累减少了约40%。
我们证明,通过改变生物分布,exoDOX的毒性低于阿霉素。