Laboratories : IAB and SyMMES - 01/10/2022 - 30/09/2025

Thesis project holders : Xavier LE GUEVEL and Didier GASPARUTTO
Young thesis researcher : Abdallah ALHALABI

Abstract: Multidimensional biophotonic nanostructures are attracting growing interest for applications in biosensing, bioimaging, implantable devices and remote therapies. This PhD research focuses on their design via the self-assembly of atomically precise gold nanoclusters (AuNCs), an emerging class of ultra-small particles (<3 nm) with size-dependent photoluminescence (PL) tunable from UV to near-infrared (370–1300 nm), combined with high photostability and biocompatibility. Their optical properties vary significantly when organized into 1D, 2D, or 3D superstructures, making them ideal for advanced biophotonic applications. DNA nanotechnology offers a versatile toolkit for directing nanomaterial self-assembly with sub-nanometer precision, from simple DNA structures (duplexes, crosses, tetrahedra) to complex DNA origami. DNA thus serves as an excellent scaffold for organizing AuNCs into multidimensional nanostructures. This work addresses the key challenge of conjugating DNA to AuNCs with controlled stoichiometry, using various chemical strategies to define the exact number of DNA strands per cluster. AuNCs of defined sizes (Au₁₈, Au₂₅, Au₂₅₀) emitting in the NIR-I (600–800 nm) and NIR-II (900–1300 nm) ranges were functionalized via ligand engineering and characterized by UV–Vis and fluorescence spectroscopy, mass spectrometry, liquid chromatography, and gel electrophoresis. Through selective hybridization, 1D, 2D and 3D (dimers, trimers, tetrahedra) AuNC structures were self-assembled with controlled interparticle spacing, achieving high yield and reproducibility. These were analyzed by gel electrophoresis, size-exclusion chromatography, electron microscopy, dynamic light scattering, and optical spectroscopy. In addition, we explored multiple chemical strategies for labeling larger DNA origami and DNA hybrid nanostructures—both by integrating the AuNC–DNA building blocks developed in this study and via direct conjugation methods such as click chemistry.
In summary, this research establishes a strong analytical and synthetic basis for high yield, high-purity fabrication of multidimensional biophotonic nanoarchitectures, offering promising prospects in biosensing, bioimaging, targeted therapy and controlled drug delivery.




Publications:
Designing atomically precise gold nanocluster architectures with DNA-guided self-assembly and biofunctionalization approaches. Alhalabi, A., Saint-Pierre, C., Boeri-Erba, E., Elchinger, P.-H., Kaur, H., Gasparutto, D., Le Guével, X., 2025. Nanoscale 17, 12775-12785. (Q1 ; IF 5.1)

Biological Templates for Gold Nanocluster Assembly : Design and Biomedical Applications. Ayed, Z., Alhalabi, A., Gasparutto, D., Le Guével, X. 2025. Aggregate. Minor revisions. (Q1 ; IF 13.7)

Programmable DNA Tetrahedra Functionalized with Atomically Precise Gold Nanoclusters. (manuscript in preparation)