Biophysical mechanisms of electroporation in cancer therapy and drug delivery

Current anticancer therapy is often constrained by low intratumoural drug penetration, systemic toxicity and limited selectivity for malignant tissue. Electroporation has therefore emerged as an important biophysical strategy: a short, intense pulsed electric fields can transiently or permanently increase membrane permeability in a controlled manner. This review analyses the physical basis of electroporation, with emphasis on induced transmembrane potential, lipid bilayer destabilisation, pore nucleation, and the transition between reversible and irreversible membrane injury. It then examines how pulse amplitude, duration, repetition, waveform, tissue conductivity, temperature and geometry determine biological outcome. Clinically, reversible electroporation underlies electrochemotherapy and several drug- and gene-delivery platforms, whereas irreversible electroporation(IRE) is used for focal tumour ablation, especially near critical vascular structures. Electroporation(EP) also remains highly relevant for non-viral delivery of DNA, RNA, proteins, and nanoparticle cargoes. Despite these advantages, treatment heterogeneity, pain, muscle contraction, secondary heating, invasive electrode placement, and the need for precise dosimetry remain serious limitations. Therefore, current research is moving towards patient-specific treatment planning, surrogate and machine-learning models for parameter optimisation. Overall, electroporation represents a strong interface between membrane biophysics and translational oncology, with growing value in both cancer therapy and advanced drug delivery.