Ultrasound targeted microbubble destruction assisted exosomal delivery of miR-21 protects the heart from chemotherapy associated cardiotoxicity

Biochem Biophys Res Commun. 2020 Oct 29;532(1):60-67. doi: 10.1016/j.bbrc.2020.05.044. Epub 2020 Aug 20.

Abstract

Chemotherapy related cardiotoxicity is now becoming one of the biggest hurdles for the prognosis of cancer patients. Therapeutically delivering protective small RNAs holds promise for the cardiotoxicity prevention and therapy. However, heart is intrinsically refractory to the nanoparticle-mediated drug delivery. In this study, we found that the exosome-mediated miRNA delivery into the heart could be significantly augmented with the aid of ultrasound targeted microbubble destruction (UTMD). Moreover, we found that UTMD assisted exosomal miR-21 delivery into the heart significantly decreased the cell death, and restored the cardiac function in a doxorubicin induced cardiotoxicity mouse model. Our study here not only provides a promising strategy to protect the heart from the chemotherapy related cardiotoxicity, but also sheds light on gene therapy of other heart diseases.

Keywords: Chemotherapy related cardiotoxicity; Exosomes; Ultrasound targeted microbubble destruction; miR-21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Apoptosis
  • Cardiotonic Agents / administration & dosage*
  • Cardiotoxicity / pathology
  • Cardiotoxicity / physiopathology
  • Cardiotoxicity / prevention & control*
  • Cell Death
  • Disease Models, Animal
  • Doxorubicin / toxicity
  • Drug Delivery Systems
  • Echocardiography, Doppler, Pulsed
  • Exosomes
  • Heart Function Tests
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • Microbubbles
  • Ultrasonics

Substances

  • Antibiotics, Antineoplastic
  • Cardiotonic Agents
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Doxorubicin