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

Luisa Pascucci, Valentina Coccè, Arianna Bonomi, Diletta Ami, Piero Ceccarelli, Emilio Ciusani, Lucia Viganò, Alberta Locatelli, Francesca Sisto, Silvia Maria Doglia, Eugenio Parati, Maria Ester Bernardo, Maurizio Muraca, Giulio Alessandri, Gianpietro Bondiolotti, Augusto Pessina

Research output: Contribution to journalArticle

221 Citations (Scopus)

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 and deliver active drugs through their MVs, suggesting the possibility of using MSCs as a factory to develop drugs with a higher cell-target specificity.

Original languageEnglish
Pages (from-to)262-270
Number of pages9
JournalJournal of Controlled Release
Volume192
DOIs
Publication statusPublished - Oct 28 2014

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Exosomes
Paclitaxel
Mesenchymal Stromal Cells
Growth
Pharmaceutical Preparations
Conditioned Culture Medium
Neoplasms
Scanning Transmission Electron Microscopy
Tumor Microenvironment
Ultracentrifugation
Vacuoles
In Vitro Techniques
Antineoplastic Agents
Electron Scanning Microscopy
High Pressure Liquid Chromatography
Cell Line
Membranes

Keywords

  • Drug delivery
  • Exosome
  • Mesenchymal stromal cells
  • Microvesicles
  • Paclitaxel

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

Cite this

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.

In: Journal of Controlled Release, Vol. 192, 28.10.2014, p. 262-270.

Research output: Contribution to journalArticle

Pascucci, L, Coccè, V, Bonomi, A, Ami, D, Ceccarelli, P, Ciusani, E, Viganò, L, Locatelli, A, Sisto, F, Doglia, SM, Parati, E, Bernardo, ME, Muraca, M, Alessandri, G, Bondiolotti, G & Pessina, A 2014, 'Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery', Journal of Controlled Release, vol. 192, pp. 262-270. https://doi.org/10.1016/j.jconrel.2014.07.042
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. / Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth : A new approach for drug delivery. In: Journal of Controlled Release. 2014 ; Vol. 192. pp. 262-270.
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AU - Ami, Diletta

AU - Ceccarelli, Piero

AU - Ciusani, Emilio

AU - Viganò, Lucia

AU - Locatelli, Alberta

AU - Sisto, Francesca

AU - Doglia, Silvia Maria

AU - Parati, Eugenio

AU - Bernardo, Maria Ester

AU - Muraca, Maurizio

AU - Alessandri, Giulio

AU - Bondiolotti, Gianpietro

AU - Pessina, Augusto

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