title: Mesenchymal stromal cells uptake and release paclitaxel without reducing its anticancer activity.
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.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mariotti
authors.forename: Renato
authors.initials: R
authors.lastname: Colognato
authors.forename: Marco
authors.initials: M
authors.lastname: Rimoldi
authors.forename: Manuela
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.forename: Valentina
authors.initials: V
authors.lastname: Cocce
authors.forename: Arianna
authors.initials: A
authors.lastname: Bonomi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Parati
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
authors.forename: Renzo
authors.initials: R
authors.lastname: Bagnati
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Italy. augusto.pessina@unimi.it.
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel