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J Control Release. 2019 May 28;302:2-18. doi: 10.1016/j.jconrel.2019.03.016. Epub 2019 Mar 16.

Microfragmented human fat tissue is a natural scaffold for drug delivery: Potential application in cancer chemotherapy.

Author information

1
Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. Electronic address: giulio.alessandri@istituto-besta.it.
2
CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
3
Laboratory of Experimental Therapy in Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
4
Clinical biochemistry and mass spectrometry lab, Dept. Health Sciences, University of Milan, Milan, Italy.
5
Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
6
Image Institute, University of Milan, Milan, Italy.
7
Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
8
Image Institute, University of Milan, Milan, Italy; School of Healthcare Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UK.
9
Section of Pathological Anatomy DMMT, University of Brescia, Brescia, Italy.
10
CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
11
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.

Abstract

Localization of chemotherapy at the tumor site can improve therapeutic efficacy and reduce systemic toxicity. In previous studies we have shown that mesenchymal stromal cells (MSCs) isolated from bone marrow or adipose tissue can be loaded with the anti-cancer drug Paclitaxel (PTX) and kill cancer cells when localized nearby. We here investigated the capacity of human micro-fragmented adipose tissue (MFAT), used as a natural scaffold of MSCs, to deliver PTX with the idea to improve local drug concentration and to prolong the therapeutic activity. Surprisingly, we found that both fresh but also devitalized MFAT (DMFAT) (by freezing/thawing procedure) were able to deliver and release significant amount of PTX, killing several human cancer cell lines in vitro with a long lasting activity. In an orthotopic mice model of Neuroblastoma (NB) transplant, DMFAT loaded with PTX prevents or delays NB relapse when placed in the surgical area of tumor resection, without any collateral toxicity. We concluded that MFAT, but also DMFAT, may represent very innovative natural biomaterials able to localize and release anti-cancer molecules at the tumor site, helping to fight cancer in human.

KEYWORDS:

Anti-cancer chemotherapy; Biomaterials; Drug delivery; Micro-fragmented adipose tissue; Natural scaffold

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