Improved Anti-Tumor Activity of Novel Highly Bioactive Liposome-Bound TRAIL in Breast Cancer Cells

Abstract

To date, no special attention had been paid to this aspect of FVP-induced TRAIL-sensitization, may be because sTRAIL used were not able to take advantage of this DR5 up-regulation. Hence, LUV-TRAIL could be a better choice than sTRAIL to be used in combination with anti-tumor drugs inducing DR5 over-expression, since LUV-TRAIL is especially effective activating this death-receptor.

High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer

“…In this line, our group previously demonstrated that human lymphocytes secrete TRAIL preferably associated with lipid vesicles called exosomes [35,36] Aiming to mimic this exosome-bound TRAIL, we generated the novel TRAIL formulation LUV-TRAIL, based on anchoring this death ligand on Large Unilamellar Vesicles (LUV) resembling these natural exosomes. LUV-TRAIL has been proved to be much more potent than soluble TRAIL both in haematological malignancies [37,38,41] and solid tumours [39,40]. Remarkably, the soluble version of TRAIL used in all those studies is virtually identical to the version used in clinical trials (Dulanermin®), which confers more significance to LUV-TRAIL improved efficiency.…”

“…Cell viability was quantified by the MTT (3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide) assay [43] as previously described [39,40]. Data was expressed as the percentage of cell viability with respect to control cells (untreated cells for sTRAIL, and cells treated with LUVs without TRAIL for LUV-TRAIL).…”

“…Clonogenic survival was assessed as previously described [40]. Quantification of the clonogenic assays was performed measuring the absorbance at 550 nm after dissolving crystal-violet with DMSO.…”

“…On this basis, we have generated artificial lipid nanoparticles containing membrane-bound TRAIL (LUV-TRAIL) resembling those natural exosomes. We already demonstrated that LUV-TRAIL was more effective inducing apoptosis than soluble TRAIL against leukemia cells that presented resistance to soluble TRAIL and chemotherapeutic drugs [37,38] and also in epithelial-derived cancer cells [39,40]. This increased cytotoxicity induced by LUV-TRAIL was due to a superior DR5 activation, which led to an enhanced DISC recruitment [40,41].…”

NanoTRAIL‐Oncology: A Strategic Approach in Cancer Research and Therapy

“…Moreover, TRAIL on glass‐supported liposomes has a substantially enhanced ability to drive the microclustering of DR4/DR5 receptors and apoptotic signaling . Inspired by this, many studies have covalently conjugated TRAIL to the surface of artificial lipid nanoparticles and achieved great results ( Figure ), such as increased tumor exposure, higher caspase activation, and improved antitumor potency in TRAIL‐resistant xenografted tumor models . Furthermore, liposome‐based TRAIL in combination with other chemotherapeutics exhibits promising preclinical results in different solid tumor models .…”