Development of an ultrasound triggered nanomedicine-microbubble complex for chemo-photodynamic-gene therapy

Nanomedicine. 2020 Jul:27:102194. doi: 10.1016/j.nano.2020.102194. Epub 2020 Apr 8.

Abstract

Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery.

Keywords: Combination therapy; Gene therapy; Nanoparticle-microbubble complex; Sonoporation; Tumor angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chlorophyllides
  • Combined Modality Therapy
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Delivery Systems
  • Drug Therapy / trends
  • Humans
  • Microbubbles
  • Nanomedicine / trends*
  • Nanoparticles / chemistry*
  • Neovascularization, Pathologic / diagnostic imaging
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy*
  • Photochemotherapy / trends
  • Porphyrins / chemistry
  • Porphyrins / pharmacology
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Reactive Oxygen Species / metabolism
  • Ultrasonography
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Chlorophyllides
  • Porphyrins
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • phytochlorin
  • Doxorubicin