Pulsed ultrasound modulates the cytotoxic effect of cisplatin and doxorubicin on cultured human retinal pigment epithelium cells (ARPE-19)

Mohammadi, S. O.; LaRocca, M. C.; Yang, C. D.; Jessen, J.; Kenney, M. C.; Lin, K. Y.

doi:10.1101/2023.10.02.560520

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bioRxiv · 10.1101/2023.10.02.560520

Pulsed ultrasound modulates the cytotoxic effect of cisplatin and doxorubicin on cultured human retinal pigment epithelium cells (ARPE-19)

Mohammadi, S. O.·LaRocca, M. C.·Yang, C. D.·Jessen, J.·Kenney, M. C.·Lin, K. Y.

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Abstract

ObjectivePulsed ultrasound has been proposed as a tool to enhance ocular drug delivery, but its effects on drug potency are not well understood. Doxorubicin-HCl and cisplatin are two drugs commonly used to treat ocular melanoma. We report the effects of pulsed ultrasound on the cytotoxicity of doxorubicin-HCl and cisplatin in vitro. MethodsCultured human retinal pigment epithelium cells (ARPE-19) cells were treated with doxorubicin-HCl or cisplatin in the presence or absence of ultrasound. MTT and Trypan blue assays were performed at 24 and 48 hours post-treatment to assess cell metabolism and death. ResultsCells treated with ultrasound plus doxorubicin-HCl demonstrated a significant decrease in metabolism compared to cells treated with doxorubicin-HCl alone. In contrast, cells treated with ultrasound plus cisplatin exhibited a significant increase in metabolism compared to cells treated with cisplatin alone at 48-hours. Cells treated with cisplatin pre-treated with ultrasound (US-Cis) exhibited a significant decrease in metabolism. Cell death was similar in doxorubicin- and cisplatin-treated cells with and without ultrasound. ConclusionPulsed ultrasound enhances the cytotoxicity of doxorubicin-HCl at 24- and 48-hours post-treatment but abrogates cisplatin toxicity 48-hours post-treatment. This suggests ultrasound modulates cell-drug interactions in a drug-specific manner. These findings may influence the future development of ultrasound-assisted ocular drug delivery systems.

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Mohammadi, S. O., LaRocca, M. C., Yang, C. D., Jessen, J., Kenney, M. C., Lin, K. Y.. 2023-10-03. Pulsed ultrasound modulates the cytotoxic effect of cisplatin and doxorubicin on cultured human retinal pigment epithelium cells (ARPE-19). https://doi.org/10.1101/2023.10.02.560520

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