Reversible Electroporation-Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With 89Zr-Labeled Reporter Nanoparticles

Mol Imaging. 2018 Jan-Dec:17:1536012117749726. doi: 10.1177/1536012117749726.

Abstract

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation-related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep.

Keywords: animal PET; drug delivery; nanoparticle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillary Permeability
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems*
  • Electroporation / methods*
  • Humans
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use
  • Positron-Emission Tomography
  • Radioisotopes / chemistry*
  • Radiopharmaceuticals / chemistry*
  • Zirconium / chemistry*

Substances

  • Radioisotopes
  • Radiopharmaceuticals
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Zirconium
  • Zirconium-89