Related Experiment Video
Updated: Mar 8, 2026
Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Comparative binding to DR4 and DR5 receptors of TRAIL and BNNTs/PAHE/mPEG-DSPE/TRAIL nanoparticles
Yves Claude Guillaume1,2,3, Claire André1,2,3
1University of Franche-Comté, Besançon, France.
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.
Insights
Nanoparticle TRAIL (NPT) delivered via boron nitride nanotubes (BNNTs) shows enhanced binding to cancer cell receptors DR4 and DR5. This nanovectorization strategy improves TRAIL
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- TRAIL (Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand) is a cytokine that induces apoptosis in cancer cells by binding to DR4 and DR5 receptors.
- Previous studies showed that nanovectorization of TRAIL using single-walled carbon nanotubes enhanced its affinity to DR5.
- Boron nitride nanotubes (BNNTs) offer a novel platform for drug delivery and biomolecule functionalization.
Purpose of the Study:
- To investigate the binding characteristics of TRAIL functionalized on BNNTs (nanoparticle TRAIL or NPT) to DR4 and DR5 receptors.
- To compare the binding affinity of NPT with soluble TRAIL to these receptors.
- To evaluate the potential of BNNT-based nanovectors for cancer therapy.
Main Methods:
- Functionalization of BNNTs with 1-pyrenebutyric acid N-hydroxysuccinimide ester to anchor TRAIL protein.
- Preparation of nanoparticle TRAIL (NPT) by mixing functionalized BNNTs with PEGylated lipids for aqueous dispersion.
- Affinity chromatography was used to study the binding of NPT and soluble TRAIL to immobilized DR4 and DR5 receptors across a temperature range (30-50°C).
Main Results:
- Negative enthalpy (ΔH) values indicated favorable van der Waals and hydrogen bonding interactions at the ligand-receptor interface.
- The binding affinities were ranked as TRAILDR4 < NPTDR4 < TRAILDR5 < NPTDR5.
- NPT exhibited higher affinity to DR4 and DR5 receptors, particularly at low pH, due to altered accessibility of the His molecular switch.
Conclusions:
- Nanovectorization of TRAIL using BNNTs significantly enhances its binding affinity to both DR4 and DR5 receptors at physiological temperature (37°C).
- The improved binding suggests that BNNT-nanovectorized TRAIL is a promising candidate for targeted cancer therapy.
- This novel nanovector system demonstrates potential for effective delivery of TRAIL to cancer cells, enhancing apoptotic signaling.
