Development of an Electroporation and Nanoparticle-based Therapeutic Platform for Bone Metastases

Marites P Melancon, Tomas Appleton Figueira, David T Fuentes, Li Tian, Yang Qiao, Jianhua Gu, Mihai Gagea, Joe E Ensor, Nina M Muñoz, Kiersten L Maldonado, Katherine Dixon, Amanda McWatters, Jennifer Mitchell, Mark McArthur, Sanjay Gupta, Alda L Tam

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Purpose: To assess for nanopore formation in bone marrow cells after irreversible electroporation (IRE) and to evaluate the antitumoral effect of IRE, used alone or in combination with doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (SPIO-DOX), in a VX2 rabbit tibial tumor model. Materials and Methods: All experiments were approved by the institutional animal care and use committee. Five porcine vertebral bodies in one pig underwent intervention (IRE electrode placement without ablation [n = 1], nanoparticle injection only [n = 1], and nanoparticle injection followed by IRE [n = 3]). The animal was euthanized and the vertebrae were harvested and evaluated with scanning electron microscopy. Twelve rabbit VX2 tibial tumors were treated, three with IRE, three with SPIO-DOX, and six with SPIO-DOX plus IRE; five rabbit VX2 tibial tumors were untreated (control group). Dynamic T2∗-weighted 4.7-T magnetic resonance (MR) images were obtained 9 days after inoculation and 2 hours and 5 days after treatment. Antitumor effect was expressed as the tumor growth ratio at T2∗-weighted MR imaging and percentage necrosis at histologic examination. Mixed-effects linear models were used to analyze the data. Results: Scanning electron microscopy demonstrated nanopores in bone marrow cells only after IRE (P < .01). Average volume of total tumor before treatment (503.1 mm3 ± 204.6) was not significantly different from those after treatment (P = .7). SPIO-DOX was identified as a reduction in signal intensity within the tumor on T2∗-weighted images for up to 5 days after treatment and was related to the presence of iron. Average tumor growth ratios were 103.0% ± 75.8 with control treatment, 154.3% ± 79.7 with SPIO-DOX, 77% ± 30.8 with IRE, and 238.5% ± 24.8 with a combination of SPIO-DOX and IRE (P = .02). The percentage residual viable tumor in bone was significantly less for combination therapy compared with control (P = .02), SPIO-DOX (P < .001), and IRE (P = .03) treatment. The percentage residual viable tumor in soft tissue was significantly less with IRE (P = .005) and SPIO-DOX plus IRE (P = .005) than with SPIO-DOX. Conclusion: IRE can induce nanopore formation in bone marrow cells. Tibial VX2 tumors treated with a combination of SPIODOX and IRE demonstrate enhanced antitumor effect as compared with individual treatments alone.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
Issue number1
StatePublished - Jan 2018


  • Animals
  • Antibiotics, Antineoplastic
  • Bone Marrow Cells
  • Bone Neoplasms
  • Doxorubicin
  • Electroporation
  • Magnetite Nanoparticles
  • Models, Biological
  • Nanopores
  • Rabbits
  • Swine
  • Tibia
  • Journal Article

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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