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Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery

Pascucci, Luisa, Coccè, Valentina, Bonomi, Arianna, Ami, Diletta, Ceccarelli, Piero, Ciusani, Emilio, Viganò, Lucia, Locatelli, Alberta, Sisto, Francesca, Doglia, Silvia Maria, Parati, Eugenio, Bernardo, Maria Ester, Muraca, Maurizio, Alessandri, Giulio, Bondiolotti, Gianpietro, Pessina, Augusto·2014·Journal of Controlled Release
DOI 10.1016/j.jconrel.2014.07.042
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Abstract

Mesenchymal stromal cells (MSCs) have been proposed for delivering anticancer agents because of their ability to home in on tumor microenvironment. We found that MSCs can acquire strong anti-tumor activity after priming with Paclitaxel (PTX) through their capacity to uptake and then release the drug. Because MSCs secrete a high amount of membrane microvesicles (MVs), we here investigated the role of MVs in the releasing mechanism of PTX. The murine SR4987 line was used as MSC model. The release of PTX from SR4987 in the conditioned medium (CM) was checked by HPLC and the anti-tumor activity of both CM and MVs was tested on the human pancreatic cell line CFPAC-1. MVs were isolated by ultracentrifugation, analyzed by transmission (TEM) and scanning electron microscopy (SEM), and the presence of PTX by the Fourier transformed infrared (FTIR) microspectroscopy. SR4987 loaded with PTX (SR4987PTX) secreted a significant amount of PTX and their CM possessed strong anti-proliferative activity on CFPAC-1. At TEM and SEM, SR4987PTX showed an increased number of "vacuole-like" structures and shed a relevant number of MVs, but did not differ from untreated SR4987. However, SR4987PTX-derived-MVs (SR4987PTX-MVs) demonstrated a strong anti proliferative activity on CFPAC-1. FTIR analysis of SR4987PTX-MVs showed the presence of an absorption spectrum in the corresponding regions of the PTX marker, absent in MVs from SR4987. Our work is the first demonstration that MSCs are able to package an…

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Metadata

Authors
Pascucci, L., Coccè, V., Bonomi, A., Ami, D., Ceccarelli, P., Ciusani, E., Viganò, L., Locatelli, A., Sisto, F., Doglia, S. M., Parati, E., Bernardo, M. E., Muraca, M., Alessandri, G., Bondiolotti, G., & Pessina, A.
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2014-10
Volume
192
Pages
262-270
ISSN
0168-3659
DOI
10.1016/j.jconrel.2014.07.042
Cited by
846
References
6
Language
en
Licence
Funders
AIRC (Associazione Italiana per la Ricerca sul Cancro) (IG-14574)

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