Abstract
Diseases involving dysfunction of smooth muscle cells present a major health and socioeconomic burden, and have remained stubbornly resistant to standard therapeutic strategies. Examples include many cardiovascular diseases and spontaneous preterm birth, a complication affecting up to 11% of all pregnancies worldwide. This fuels the continued search for new drug delivery strategies to treat these conditions. The use of cell penetrating peptides (CPPs) for this purpose remains a promising, if as yet unrealized, avenue to explore. In part, this may relate to a paucity of studies investigating the application of CPPs as drug delivery vectors to human smooth muscle cells and tissues. We have sought to address this knowledge gap by reporting methods for examining the uptake of different CPP-cargo vectors to human uterine and vascular smooth muscle cells. In particular, we report here (a) that four different CPP-fluorophore conjugates, spanning masses of 1309–3435 Da, and net charges of +2 to +7, can be delivered to human isolated uterine smooth muscle cells without inducing cell toxicity; (b) that the cargo delivered by such CPPs can be fluorescent moieties and/or biologically active peptides; (c) that CPP delivery in a short time frame to native smooth muscle cells in human tissues ex vivo can be achieved. Further exploration of CPPs as tools to facilitate targeted drug delivery to native human smooth muscle tissues will assist in improving our understanding of scientific mechanisms underlying major diseases involving smooth muscle dysfunction as well as facilitating therapeutic investigations.
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This work was supported by Wellbeing of Women (RTF 376).
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1 Electronic Supplementary Materials
Video 1
Indicating mobility of Pen-rhodamine (red) in human uterine smooth muscle cells (nucleus in blue). (MP4 523 kb)
Video 2
Indicating mobility of Pen-NBD-rhodamine in human uterine smooth muscle cells (nucleus in blue). (MP4 67 kb)
Video 3
Indicating localization of Pen-rhodamine (red) in relation to (a) mitochondria (green) and (b) nucleus (blue) within human uterine smooth muscle cells. (MP4 5661 kb)
Video 4
Animation of Z-stack series of microscope images of human uterine smooth muscle cells demonstrating intracellular uptake of Pen-rhodamine (red). (MP4 1766 kb)
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Gurney, L., Robson, S.C., Sweeney, M., Jones, A.T., Taggart, M.J. (2022). Strategies for Peptide-Mediated Cargo Delivery to Human Smooth Muscle Cells. In: Langel, Ü. (eds) Cell Penetrating Peptides. Methods in Molecular Biology, vol 2383. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1752-6_29
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DOI: https://doi.org/10.1007/978-1-0716-1752-6_29
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