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

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