Electric Fields in Tumors Exposed to External Voltage Sources: Implication for Electric Field-Mediated Drug and Gene Delivery
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
The intratumoral field, which determines the efficiency of electric field-mediated drug and gene delivery, can differ significantly from the applied field. Therefore, we investigated the distribution of the electric field in mouse tumors and tissue phantoms exposed to a large range of electric stimuli, and quantified the resistances of tumor, skin, and electrode-tissue interface. The samples used in the study included 4T1 and B16.F10 tumors, mouse skin, and tissue phantoms constructed with 1% agarose gel with or without 4T1 cells. When pulsed electric fields were applied to samples using a pair of parallel-plate electrodes, we determined the electric field and resistances in each sample as well as the resistance at the electrode-tissue interface. The electric fields in the center region of tissue phantoms and tumor slices ex vivo were macroscopically uniform and unidirectional between two parallel-plate electrodes. The field strengths in tumor tissues were significantly lower than the applied field under both ex vivo and in vivo conditions. During in vivo stimulation, the ratio of intratumoral versus applied fields was approximately either 20% or 55%, depending on the applied field. Meanwhile, the total resistance of skin and electrode-tissue interface was decreased by approximately 70% and the electric resistance at the center of both tumor models was minimally changed when the applied field was increased from 50 to 400 V/cm. These results may be useful for improving electric field-mediated drug and gene delivery in solid tumors.
- Brummer, S. B., and M. J. Turner. Electrical stimulation with Pt electrodes: II-estimation of maximum surface redox (theoretical non-gassing) limits. IEEE Trans. Biomed. Eng. 24:440–443, 1977.
- Brummer, S. B., and M. J. Turner. Electrochemical considerations for safe electrical stimulation of the nervous system with platinum electrodes. IEEE Trans. Biomed. Eng. 24:59–63, 1977.
- Bureau, M. F., J. Gehl, V. Deleuze, L. M. Mir, and D. Scherman. Importance of association between permeabilization and electrophoretic forces for intramuscular DNA electrotransfer. Biochim. Biophys. Acta 1474:353–359, 2000.
- Canatella, P. J., M. M. Black, D. M. Bonnichsen, C. McKenna, and M. R. Prausnitz. Tissue electroporation: quantification and analysis of heterogeneous transport in multicellular environments. Biophys. J. 86:3260–3268, 2004.
- Canatella, P. J., J. F. Karr, J. A. Petros, and M. R. Prausnitz. Quantitative study of electroporation-mediated molecular uptake and cell viability. Biophys. J. 80:755–764, 2001. CrossRef
- Cemazar, M., I. Wilson, G. U. Dachs, G. M. Tozer, and G. Sersa. Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy—spatial and time dependent distribution. BMC Cancer. 4:81, 2004. CrossRef
- DeBruin, K. A., and W. Krassowska. Modeling electroporation in a single cell. I. Effects Of field strength and rest potential. Biophys. J. 77:1213–1224, 1999.
- Dorgan, S. J., and R. B. Reilly. A model for human skin impedance during surface functional neuromuscular stimulation. IEEE Trans. Rehabil. Eng. 7:341–348, 1999. CrossRef
- Gu, W. Y., and M. A. Justiz. Apparatus for measuring the swelling dependent electrical conductivity of charged hydrated soft tissues. J. Biomech. Eng. 124:790–793, 2002. CrossRef
- Gu, W. Y., W. M. Lai, and V. C. Mow. Transport of fluid and ions through a porous-permeable charged-hydrated tissue, and streaming potential data on normal bovine articular cartilage. J. Biomech. 26:709–723, 1993. CrossRef
- Heller, L., M. J. Jaroszeski, D. Coppola, C. Pottinger, R. Gilbert, and R. Heller. Electrically mediated plasmid DNA delivery to hepatocellular carcinomas in vivo. Gene. Ther. 7:826–829, 2000. CrossRef
- Heller, R., R. Gilbert, and M. J. Jaroszeski. Electrochemotherapy: An emerging drug delivery method for the treatment of cancer. Adv. Drug Deliv. Rev. 26:185–197, 1997. CrossRef
- Jadoul, A., J. Bouwstra, and V. V. Preat. Effects of iontophoresis and electroporation on the stratum corneum. Review of the biophysical studies. Adv. Drug Deliv. Rev. 35:89–105, 1999. CrossRef
- Kotnik, T., and D. Miklavcic. Analytical description of transmembrane voltage induced by electric fields on spheroidal cells. Biophys. J. 79:670–679, 2000.
- Krol, A., M. W. Dewhirst, and F. Yuan. Effects of cell damage and glycosaminoglycan degradation on available extravascular space of different dextrans in a rat fibrosarcoma. Int. J. Hyperthermia. 19:154–164, 2003. CrossRef
- Krol, A., J. Maresca, M. W. Dewhirst, and F. Yuan. Available volume fraction of macromolecules in the extravascular space of a fibrosarcoma: Implications for drug delivery. Cancer Res. 59:4136–4141, 1999.
- Lohr, F., D. Y. Lo, D. A. Zaharoff, K. Hu, X. Zhang, Y. Li, Y. Zhao, M. W. Dewhirst, F. Yuan, and C. Y. Li. Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation. Cancer Res. 61:3281–3214, 2001.
- Lucas, M. L., L. Heller, D. Coppola, and R. Heller. IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma. Mol. Ther. 5:668–675, 2002. CrossRef
- Mir, L. M. Therapeurtic perspectives on in vivo cell electropermeabilization. Bioelectrochemistry 53:1–10, 2000. CrossRef
- Mossop, B. J., R. C. Barr, D. A. Zaharoff, and F. Yuan. Electric fields within cells as a function of membrane resistivity–a model study. IEEE Trans. Nanobioscience 3:225–231, 2004. CrossRef
- Neumann, E., S. Kakorin, and K. Toensing. Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem. Bioenerg. 48:3–16, 1999. CrossRef
- Niidome, T., and L. Huang. Gene therapy progress and prospects: nonviral vectors. Gene. Ther. 9:1647–1652, 2002. CrossRef
- Nishikawa, M., and L. Huang. Nonviral vectors in the new millennium: Delivery barriers in gene transfer. Hum. Gene Ther. 12:861–870, 2001. CrossRef
- Panescu, D., J. G. Webster, and R. A. Stratbucker. A nonlinear finite element model of the electrode-electrolyte-skin system. IEEE Trans. Biomed. Eng. 41:681–687, 1994. CrossRef
- Pavlin, M., and D. Miklavcic. Effective conductivity of a suspension of permeabilized cells: a theoretical analysis. Biophys. J. 85:719–729, 2003.
- Pavselj, N., Z. Bregar, D. Cukjati, D. Batiuskaite, L. M. Mir, and D. Miklavcic. The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals. IEEE Trans. Biomed. Eng. 52:1373–1381, 2005. CrossRef
- Prausnitz, M. R., V. G. Bose, R. Langer, and J. C. Weaver. Electroporation of mammalian skin: A mechanism to enhance transdermal drug delivery. Proc. Natl. Acad. Sci. USA 90:10504–10508, 1993. CrossRef
- Sel, D., D. Cukjati, D. Batiuskaite, T. Slivnik, L. M. Mir, and D. Miklavcic. Sequential finite element model of tissue electropermeabilization. IEEE Trans. Biomed. Eng. 52:816–827, 2005. CrossRef
- Sersa, G., M. Cemazar, and D. Miklavcic. Antitumor effectiveness of electrochemotherapy with cis-diamminedichl-oroplatinum(II) in mice. Cancer Res. 55:3450–3455, 1995.
- Zaharoff, D. A., R. C. Barr, C. Y. Li, and F. Yuan. Electromobility of plasmid DNA in tumor tissues during electric field-mediated gene delivery. Gene Ther. 9:1286–1290, 2002. CrossRef
- Zaharoff, D. A., and F. Yuan. Effects of pulse strength and pulse duration on in vitro DNA electromobility. Bioelectrochemistry 62:37–45, 2004. CrossRef
- Electric Fields in Tumors Exposed to External Voltage Sources: Implication for Electric Field-Mediated Drug and Gene Delivery
Annals of Biomedical Engineering
Volume 34, Issue 10 , pp 1564-1572
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- Drug and gene delivery
- Industry Sectors
- Author Affiliations
- 1. Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, 27708, USA
- 2. Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD, 20892, USA