title: Comparative binding to DR4 and DR5 receptors of TRAIL and BNNTs/PAHE/mPEG-DSPE/TRAIL nanoparticles.
abstract: TRAIL is a member of the tumor necrosis factor family of cytokines, which induces apoptosis of cancer cells, thanks to its binding to its cognate receptors DR5 and DR4. We have recently demonstrated that nanovectorization of TRAIL with single-walled carbon nanotubes enhanced TRAIL affinity to DR5. In this paper, 1-pyrenebutyric acid N-hydroxysuccinimide ester functionalized boron nitride nanotubes (BNNTs) were used to anchor the TRAIL protein. The resulting BNNT/1-pyrenebutyric acid N-hydroxysuccinimide ester nanotubes were mixed with methoxy-poly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-conjugates so as to allow a good dispersion of these nanoparticle TRAIL (NPT) in aqueous solution. The difference of binding between NPT and soluble TRAIL to DR4 and DR5 receptors was then studied by the use of affinity chromatography. DR4 and DR5 receptors were thus immobilized on a chromatographic support, and the binding of the 2 ligands TRAIL and NPT to DR4 and DR5 was studied in the temperature range 30°C to 50°C. Negative enthalpy (ΔH) values indicated that van der Waals interactions and hydrogen bonding are engaged favorably at the ligand-receptor interface. It was shown that their rank-ordered affinities were strongly different in the sequence TRAILDR4< NPTDR4< TRAILDR5< NPTDR5, and the highest affinity for NPT to DR4 and DR5 receptors observed at low pHs was due to the less accessibility of the His molecular switch to be protonated when TRAIL was immobilized on BNNTs. Taken together, our results demonstrated that nanovectorization of TRAIL with BNNTs enhanced its binding to both DR4 and DR5 receptors at 37°C. Our novel nanovector could potentially be used for delivering TRAIL to cells for cancer treatment.
authors.affiliation: University of Franche-Comté, Besançon, France.|EA481 Neurosciences Intégratives et Cliniques/Pôle Chimie Analytique Bioanalytique et Physique (PNCABP), Besançon, France.|CHRU Besançon, Pôle Pharmaceutique, Besançon, France.
authors.forename: Yves Claude
authors.initials: YC
authors.lastname: Guillaume
authors.affiliation: University of Franche-Comté, Besançon, France.|EA481 Neurosciences Intégratives et Cliniques/Pôle Chimie Analytique Bioanalytique et Physique (PNCABP), Besançon, France.|CHRU Besançon, Pôle Pharmaceutique, Besançon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: André
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011721:Pyrenes / Q000138:chemical synthesis / Q000737:chemistry; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000235:genetics; D014867:Water / Q000737:chemistry
chemical_list: D037742:Nanotubes, Carbon; D011721:Pyrenes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014867:Water; C002218:1-pyrenebutyrate
keywords: BNNTs; HPLC; TRAIL; binding; death receptors; thermodynamic