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Int. J. Mol. Sci. 2018, 19(5), 1449; https://doi.org/10.3390/ijms19051449

Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma

1
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain
2
Instituto de Investigación Sanitaria de Aragón (ISS), 50009 Zaragoza, Spain
3
Cell Death, Cancer and Inflammation, University College of London, London WC1E 6BT, UK
4
Servicio de Inmunología, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
5
Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, 50009 Zaragoza, Spain
6
Instituto de Nanociencia de Aragón, 50009 Zaragoza, Spain
*
Author to whom correspondence should be addressed.
Received: 15 April 2018 / Revised: 29 April 2018 / Accepted: 11 May 2018 / Published: 13 May 2018
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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Abstract

Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells. Only few clinical trials have used TRAIL-based treatments in sarcoma, but they show only low or moderate efficacy of TRAIL. Consequently, novel TRAIL formulations with an improved TRAIL bioactivity are necessary. Our group has developed a novel TRAIL formulation based on tethering this death ligand on a lipid nanoparticle surface (LUV-TRAIL) resembling the physiological secretion of TRAIL as a trasmembrane protein inserted into the membrane of exosomes. We have already demonstrated that LUV-TRAIL shows an improved cytotoxic activity when compared to soluble recombinant TRAIL both in hematological malignancies and epithelial-derived cancers. In the present study, we have tested LUV-TRAIL in several human sarcoma tumor cell lines with different sensitivity to soluble recombinant TRAIL, finding that LUV-TRAIL was more efficient than soluble recombinant TRAIL. Moreover, combined treatment of LUV-TRAIL with distinct drugs proved to be especially effective, sensitizing even more resistant cell lines to TRAIL. View Full-Text
Keywords: sarcoma; TRAIL; flavopiridol; immunotherapy; lipid nanoparticles sarcoma; TRAIL; flavopiridol; immunotherapy; lipid nanoparticles
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Gallego-Lleyda, A.; De Miguel, D.; Anel, A.; Martinez-Lostao, L. Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma. Int. J. Mol. Sci. 2018, 19, 1449.

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