Abstract
To improve the drug delivery efficiency on target cells, many strategies have been developed including Mesenchymal Stromal Cells (MSCs) approaches. In a previous study, we found that bone-marrow-derived MSCs (BM-MSCs) were able to incorporate and release the anti-tumor and anti-angiogenic drug, Paclitaxel (PTX). In this study, we evaluated the stability of PTX in standard cell culture conditions by analyzing the metabolites produced by MSCs after their incorporation of the drug. We are able to show that MSCs do not release either 3-OH-PTX or 6-OH-PTX metabolites (having a lower anticancer activity) but release an active PTX molecule together with the isomer 7-Epitaxol, is known to maintain the whole biological activity. This confirms that the simple procedure of MSCs priming with a drug (without any genetic cell manipulation), in our case PTX, does not modify the activity of the molecule and provides a new biological-device to carry and deliver PTX in tumor sites, by contributing to improve drug efficacy and target selectivity in cancer therapy.
Keywords: Anti-tumor activity, cancer, drug delivery, mesenchymal stromal cell, paclitaxel.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Mesenchymal Stromal Cells Uptake and Release Paclitaxel without Reducing its Anticancer Activity
Volume: 15 Issue: 3
Author(s): Massimo Mariotti, Renato Colognato, Marco Rimoldi, Manuela Rizzetto, Francesca Sisto, Valentina Cocce, Arianna Bonomi, Eugenio Parati, Giulio Alessandri, Renzo Bagnati and Augusto Pessina
Affiliation:
Keywords: Anti-tumor activity, cancer, drug delivery, mesenchymal stromal cell, paclitaxel.
Abstract: To improve the drug delivery efficiency on target cells, many strategies have been developed including Mesenchymal Stromal Cells (MSCs) approaches. In a previous study, we found that bone-marrow-derived MSCs (BM-MSCs) were able to incorporate and release the anti-tumor and anti-angiogenic drug, Paclitaxel (PTX). In this study, we evaluated the stability of PTX in standard cell culture conditions by analyzing the metabolites produced by MSCs after their incorporation of the drug. We are able to show that MSCs do not release either 3-OH-PTX or 6-OH-PTX metabolites (having a lower anticancer activity) but release an active PTX molecule together with the isomer 7-Epitaxol, is known to maintain the whole biological activity. This confirms that the simple procedure of MSCs priming with a drug (without any genetic cell manipulation), in our case PTX, does not modify the activity of the molecule and provides a new biological-device to carry and deliver PTX in tumor sites, by contributing to improve drug efficacy and target selectivity in cancer therapy.
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Mariotti Massimo, Colognato Renato, Rimoldi Marco, Rizzetto Manuela, Sisto Francesca, Cocce Valentina, Bonomi Arianna, Parati Eugenio, Alessandri Giulio, Bagnati Renzo and Pessina Augusto, Mesenchymal Stromal Cells Uptake and Release Paclitaxel without Reducing its Anticancer Activity, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (3) . https://dx.doi.org/10.2174/1871520614666140618113441
DOI https://dx.doi.org/10.2174/1871520614666140618113441 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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