Electric fields to enhance drug delivery to non-superficial tumors

Tissue penetration of anticancer drugs is hindered by adverse biophysical properties of solid tumors, including elevated interstitial fluid pressure, dense extracellular matrices, and abnormal vascular architecture. The use of electric fields can enhance drug transport and overcome these physical barriers, yet their clinical use is limited to superficial tumors such as melanoma and head & neck cancer. Here, we review current knowledge on electrically enhanced drug delivery approaches for non-superficial tumors, including electromotive drug administration (EMDA), iontophoresis, electrochemotherapy, tumor treating fields (TTF), and electrostatic precipitation (ESP) of intraperitoneal aerosols. The underlying electrokinetic mechanisms - electromigration, electroosmosis, and electroporation - are discussed together with the electrical properties of tumor tissue that influence electric field distribution and transport processes. Preclinical and clinical evidence demonstrates that these techniques can significantly increase tissue penetration of anticancer agents and improve therapeutic outcomes in selected indications. EMDA has been successfully applied in intravesical therapy for bladder cancer and shows promise for intraperitoneal drug delivery. Implantable iontophoretic systems represent an emerging strategy for localized treatment of dense stromal tumors such as pancreatic cancer and glioblastoma. Electrochemotherapy has already entered clinical practice for cutaneous tumors and is increasingly explored for deep-seated malignancies. Tumor treating fields, currently approved for glioblastoma and mesothelioma, may also enhance cellular drug uptake. Finally, ESP improves spatial distribution and tissue penetration of aerosolized intraperitoneal chemotherapy. Collectively, these technologies illustrate the potential of electric fields to modulate drug transport in tumor tissue. Further research will be essential to fully exploit electrically assisted drug delivery in oncology.