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Int. J. Mol. Sci. 2018, 19(5), 1449;

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

Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (ISS), 50009 Zaragoza, Spain
Cell Death, Cancer and Inflammation, University College of London, London WC1E 6BT, UK
Servicio de Inmunología, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, 50009 Zaragoza, Spain
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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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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