Electroporation-induced changes in tumor vasculature and microenvironment can promote the delivery and increase the efficacy of sorafenib nanoparticles Journal Article
| Authors: | Kodama, H.; Shamay, Y.; Kimura, Y.; Shah, J.; Solomon, S. B.; Heller, D.; Srimathveeravalli, G. |
| Article Title: | Electroporation-induced changes in tumor vasculature and microenvironment can promote the delivery and increase the efficacy of sorafenib nanoparticles |
| Abstract: | Blood vessels, the extracellular space, and the cell membrane represent physiologic barriers to nanoparticle-based drug delivery for cancer therapy. We demonstrate that electroporation (EP) can assist in the delivery of dye stabilized sorafenib nanoparticles (SFB-IR783) by increasing the permeability of endothelial monolayers, improving diffusion through the extracellular space in tumorspheres, and by disrupting plasma membrane function in cancer cells. These changes occur in a dose-dependent fashion, increasing proportionally with electric field strength. Cell death from irreversible electroporation (IRE) was observed to contribute to the persistent transport of SFB-IR783 through these physiologic barriers. In a model of mice bearing bilateral xenograft HCT116 colorectal tumors, treatment with EP resulted in the immediate and increased uptake of SFB-IR783 when compared with the untreated contralateral tumor. The uptake of SFB-IR783 was independent of direct transfection of cells through EP and was mediated by changes in vascular permeability and extracellular diffusion. The combination of EP and SFB-IR783 was observed to result in 40% reduction in mean tumor diameter when compared with sham treatment (p < .05) at the time of sacrifice, which was not observed in cohorts treated with EP alone or SFB-IR783 alone. Treatment of tumor with EP can augment the uptake and increase the efficacy of nanoparticle therapy. © 2019 |
| Keywords: | cell death; endothelial cells; tumors; cell membranes; electroporation; nanoparticles; body fluids; molecular biology; mammals; diseases; extracellular space; blood vessels; targeted drug delivery; tumor vasculature; vascular permeability; controlled drug delivery; electric fields; microenvironments; colorectal tumors; electric field strength; extracellular diffusion; membrane functions |
| Journal Title: | Bioelectrochemistry |
| Volume: | 130 |
| ISSN: | 1567-5394 |
| Publisher: | Elsevier BV |
| Date Published: | 2019-12-01 |
| Start Page: | 107328 |
| Language: | English |
| DOI: | 10.1016/j.bioelechem.2019.107328 |
| PROVIDER: | scopus |
| PUBMED: | 31306879 |
| PMCID: | PMC6859646 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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