title: Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models.
abstract: OBJECTIVE
  To demonstrate that exosomes (exo) could increase the therapeutic index of doxorubicin (DOX).
  
  
  METHODS
  Exosomes were characterized by nanoparticle tracking analysis and western blot. Tissue toxicity was evaluated by histopathological analysis and drug efficacy by measuring tumor volume. DOX biodistribution was analyzed by MS.
  
  
  RESULTS
  Exosomal doxorubicin (exoDOX) avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells. For this reason, mice can be treated with higher concentration of exoDOX thus increasing the efficacy of DOX as demonstrated in breast and ovarian mouse tumors.
  
  
  CONCLUSIONS
  ExoDOX is safer and more effective than free DOX. Importantly, the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer was utilized for providing a new therapeutic opportunity.
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.|Doctoral School in Pharmacological Sciences, University of Padua, Padua, Italy.
authors: Mohamad
authors: M
authors: Hadla
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.|Doctoral School in Nanotechnology, University of Trieste, Trieste, Italy.
authors: Stefano
authors: S
authors: Palazzolo
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
authors: Giuseppe
authors: G
authors: Corona
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
authors: Isabella
authors: I
authors: Caligiuri
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
authors: Vincenzo
authors: V
authors: Canzonieri
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
authors: Giuseppe
authors: G
authors: Toffoli
authors: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.
authors: Flavio
authors: F
authors: Rizzolio
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D055354:Exosomes / Q000737:chemistry; D005260:Female; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D004317:Doxorubicin
keywords: breast and ovarian cancers; doxorubicin; drug delivery; exosomes; therapeutic index