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Article

Limited Efficacy of Nanoparticle-Assisted Electroporation for Membrane Permeabilization and Gene Electrotransfer

1
Faculty of Electrical Engineering, University of Ljubljana, Tržaška 25, 1000 Ljubljana, Slovenia
2
Department for Materials Synthesis, Jožef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia
3
Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia
4
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
5
Faculty of Bioengineering, University of Genova, Via All’Opera Pia 13, 16145 Genova, Italy
*
Author to whom correspondence should be addressed.
Pharmaceutics 2025, 17(8), 964; https://doi.org/10.3390/pharmaceutics17080964
Submission received: 17 June 2025 / Revised: 11 July 2025 / Accepted: 19 July 2025 / Published: 25 July 2025
(This article belongs to the Special Issue Nanoparticle-Based Gene Delivery)

Abstract

Background/Objectives: Nanoparticles (NPs) were previously explored as enhancers in electroporation due to their potential to locally amplify electric fields near cell membranes, with gold nanoparticles (AuNPs) in particular showing promise in improving membrane permeability and gene electrotransfer (GET). In this study, we systematically investigated the influence of NP properties—including size, shape, surface functionalization, and material—on electroporation efficacy. Methods: A combined approach using theoretical modeling and experimental validation was employed, encompassing numerical simulations, membrane permeabilization assays, transmission electron microscopy, and GET efficiency measurements. Results: Numerical results revealed that the presence of NPs alters local electric field distributions, but the amplification is highly localized, regardless of NP conductivity or geometry. Experimentally, only two out of six tested NP types produced a statistically significant, yet modest, increase in membrane permeability at one electric field intensity. Similarly, GET improvement was observed with only one NP type, with no dependence on concentration or functionalization. Conclusions: Overall, our findings demonstrate that NPs, under tested conditions, do not substantially enhance cell membrane permeability or GET efficacy. These conclusions are supported by both computational modeling and in vitro experiments.
Keywords: nanoparticles; electroporation; numerical model; permeabilization; gene electrotransfer nanoparticles; electroporation; numerical model; permeabilization; gene electrotransfer

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MDPI and ACS Style

Polajžer, T.; Kranjc, M.; Kralj, S.; Caf, M.; Romih, R.; Hudoklin, S.; Rocca, F.; Miklavčič, D. Limited Efficacy of Nanoparticle-Assisted Electroporation for Membrane Permeabilization and Gene Electrotransfer. Pharmaceutics 2025, 17, 964. https://doi.org/10.3390/pharmaceutics17080964

AMA Style

Polajžer T, Kranjc M, Kralj S, Caf M, Romih R, Hudoklin S, Rocca F, Miklavčič D. Limited Efficacy of Nanoparticle-Assisted Electroporation for Membrane Permeabilization and Gene Electrotransfer. Pharmaceutics. 2025; 17(8):964. https://doi.org/10.3390/pharmaceutics17080964

Chicago/Turabian Style

Polajžer, Tamara, Matej Kranjc, Slavko Kralj, Maja Caf, Rok Romih, Samo Hudoklin, Federica Rocca, and Damijan Miklavčič. 2025. "Limited Efficacy of Nanoparticle-Assisted Electroporation for Membrane Permeabilization and Gene Electrotransfer" Pharmaceutics 17, no. 8: 964. https://doi.org/10.3390/pharmaceutics17080964

APA Style

Polajžer, T., Kranjc, M., Kralj, S., Caf, M., Romih, R., Hudoklin, S., Rocca, F., & Miklavčič, D. (2025). Limited Efficacy of Nanoparticle-Assisted Electroporation for Membrane Permeabilization and Gene Electrotransfer. Pharmaceutics, 17(8), 964. https://doi.org/10.3390/pharmaceutics17080964

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