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

被引:30
作者
Alessandri, Giulio [1 ]
Cocce, Valentina [2 ]
Pastorino, Fabio [3 ]
Paroni, Rita [4 ]
Cas, Michele Dei [4 ]
Restelli, Francesco [5 ]
Pollo, Bianca [6 ]
Gatti, Laura [1 ]
Tremolada, Carlo [6 ,7 ]
Berenzi, Angiola [8 ]
Parati, Eugenio [1 ]
Brini, Anna Teresa [2 ,9 ]
Bondiolotti, Gianpietro [10 ]
Ponzoni, Mirco [3 ]
Pessina, Augusto [2 ]
机构
[1] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Cellular Neurobiol Lab, Via Celoria 11, I-20131 Milan, Italy
[2] Univ Milan, Dept Biomed Surg & Dent Sci, CRC StaMeTec, Milan, Italy
[3] IRCCS Ist Giannina Gaslini, Lab Expt Therapy Oncol, Genoa, Italy
[4] Univ Milan, Dept Hlth Sci, Clin Biochem & Mass Spectrometry lab, Milan, Italy
[5] Fdn IRCCS Ist Neurol Carlo Besta, Dept Neurosurg, Milan, Italy
[6] Univ Milan, Image Inst, Milan, Italy
[7] Manchester Metropolitan Univ, Sch Healthcare Sci, John Dalton Bldg,Chester St, Manchester M1 5GD, Lancs, England
[8] Univ Brescia, Sect Pathol Anat DMMT, Brescia, Italy
[9] IRCCS Ist Ortoped Galeazzi, Milan, Italy
[10] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy
关键词
Micro-fragmented adipose tissue; Anti-cancer chemotherapy; Drug delivery; Natural scaffold; Biomaterials; MESENCHYMAL STROMAL CELLS; ADIPOSE-TISSUE; PACLITAXEL; PHARMACOKINETICS; GROWTH; MICROENVIRONMENT; NANOCARRIERS; TOXICITY; CULTURE;
D O I
10.1016/j.jconrel.2019.03.016
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:2 / 18
页数:17
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