Gilles Bruylants

Beyond citrate stabilization, calix[4]arene-coated gold nanoparticles provide a robust platform for thiol-mediated surface functionalization, enabling straightforward conjugation of thiolated oligonucleotides.

The development of sensors capable of selectively detecting polyamines in aqueous environments is crucial for early and noninvasive disease diagnostics. These aliphatic cations participate in fundamental cellular processes, and their dysregulation has been linked to several cancers and neurodegenerative disorders. Although conventional detection methods, such as chromatography and mass spectrometry, offer excellent sensitivity, their complexity, cost, and limited portability restrict their use in rapid or point‐of‐care testing. This work presents a colorimetric nanosensor based on gold nanoparticles (AuNPs) functionalized with a p ‐tert‐butyl‐calix[5]arene derivative ( Calix[5] ), a supramolecular receptor with selectivity for primary alkylammonium ions imparted by intracavity host–guest complexation. The molecular recognition event induces interparticle bridging, triggering nanoparticle aggregation that manifests as a visible color change of the suspension. The system exhibits remarkable chain‐length‐dependent selectivity: long polyammonium chains, such as 1,12‐dodecanediammonium and the biogenic polyamine spermine, induce rapid (< 5 min) nanoparticle aggregation, resulting in a distinct plasmonic shift. In contrast, shorter analogues (spermidine, 1,6‐hexadiammonium) show negligible responses. These findings demonstrate a simple, rapid, and cost‐effective approach for the selective sensing of structurally defined polyamines, with potential applications in noninvasive biomarker monitoring.

Plasmon irradiation enables reductive grafting of calix[4]arene diazonium salts onto AuNPs, leading to dense and stable coatings.

Selective proteolysis remains a significant challenge with relevance to industrial and pharmaceutical applications, motivating development of chemical strategies emulating the specificity of natural proteases. Here, we report that the discrete Zr‐oxo nanocluster‐based solid, [Zr₁₇O₈(OH)₂₄(OH₂)₁₂(HCO₂)₁₂(SO₄)₈] · 6 HCl · 30 H₂O (Zr₁₇) serves as an efficient, recyclable heterogeneous catalyst for site‐selective proteolysis with tunable fragment selectivity. A combination of solution‐ and solid‐state NMR spectroscopy highlighted the importance of the ligand environment of solid Zr₁₇ for enabling efficient protein‐cluster interaction and controlling reactivity. We demonstrate that Zr₁₇ achieves a proteolytic performance comparable to natural enzymes while allowing fine modulation of peptide product profiles by adjusting reaction parameters. Substrate adsorption and product desorption were found to be governed by the net charge of both catalyst and substrate, as well as rapid reorganization of the cluster's capping ligands, according to UV‐Vis/IR spectroscopy and isothermal titration calorimetry. Crucially, the insoluble nature and excellent stability of Zr₁₇, evidenced by pair distribution function analysis, allowed reuse across multiple catalytic cycles, overcoming a major limitation of proteolytic systems. This study reveals how cluster surface chemistry governs substrate interaction and catalysis, guiding rational design of next‐generation cluster‐based catalysts, including hybrid materials such as metal‐organic frameworks.

Selective proteolysis remains a significant challenge with relevance to industrial and pharmaceutical applications, motivating development of chemical strategies emulating the specificity of natural proteases. Here, we report that the discrete Zr‐oxo nanocluster‐based solid, [Zr₁₇O₈(OH)₂₄(OH₂)₁₂(HCO₂)₁₂(SO₄)₈] · 6 HCl · 30 H₂O (Zr₁₇) serves as an efficient, recyclable heterogeneous catalyst for site‐selective proteolysis with tunable fragment selectivity. A combination of solution‐ and solid‐state NMR spectroscopy highlighted the importance of the ligand environment of solid Zr₁₇ for enabling efficient protein‐cluster interaction and controlling reactivity. We demonstrate that Zr₁₇ achieves a proteolytic performance comparable to natural enzymes while allowing fine modulation of peptide product profiles by adjusting reaction parameters. Substrate adsorption and product desorption were found to be governed by the net charge of both catalyst and substrate, as well as rapid reorganization of the cluster's capping ligands, according to UV‐Vis/IR spectroscopy and isothermal titration calorimetry. Crucially, the insoluble nature and excellent stability of Zr₁₇, evidenced by pair distribution function analysis, allowed reuse across multiple catalytic cycles, overcoming a major limitation of proteolytic systems. This study reveals how cluster surface chemistry governs substrate interaction and catalysis, guiding rational design of next‐generation cluster‐based catalysts, including hybrid materials such as metal‐organic frameworks.

This study introduces an innovative plasmon-mediated strategy for the surface functionalization of colloidal gold nanoparticles (AuNPs) through the reductive grafting of calix[4]arene-based tetra-diazonium salts under pulsed laser irradiation. By exploiting the localized surface plasmon resonance (LSPR) of AuNPs, the diazonium salts were efficiently grafted onto the nanoparticle surface without the use of external reducing agents or photocatalysts. Optimization of experimental parameters, such as irradiation wavelength, power, and reaction time, enabled rapid and robust functionalization while minimizing nanoparticle degradation. Mechanistic studies confirmed that both hot electron generation and localized photothermal effects contribute to the grafting process. The method was successfully extended to other diazonium salts, with calix[4]arene derivatives yielding densely packed, highly stable organic shells. Compared to conventional chemical reduction, this laser-assisted approach significantly reduces reaction time and reagent consumption. Overall, the method provides a fast, efficient, and versatile strategy for the covalent functionalization of plasmonic nanoparticles in suspension.

Gold-based nanomaterials have marked the last few decades with the emergence of new medical technologies presenting unique features. For instance, the conjugation of gold nanoparticles (AuNPs) and nucleic acids has allowed the creation of nanocarriers with immense promise for gene therapy applications. Although the use of lipid particles as RNA delivery vectors has been broadly explored, this review aims to focus on the limited models reported for the conjugation of RNA with AuNPs. This is nonetheless unexpected regarding the manifold strategies existing to conjugate DNA to gold nanoparticles, which are exhaustively listed in this paper. Furthermore, new processes such as fast microwave and freezing methods have been described very recently, and it therefore seemed necessary to review these recent but promising conjugation pathways and to pick out those applicable to RNA. Indeed, RNA is considerably more attractive than DNA for therapeutic purposes, but its low stability involves numerous difficulties in the construction of effective nanodevices. However, from the many approaches developed for DNA, it turns out that just two of them are frequently used for the building of RNA delivery platforms based on gold: the salt-aging method with thiolated RNA strands and physisorption. However, both approaches present strong limitations such as the low stability of the Au–S bond and the potential cytotoxicity of polycations. To conclude, this general assessment highlights that the exploration of innovating approaches implying different chemistries is needed for the creation of more robust and shapeable AuNPs-RNA conjugates.

Nanoparticle technology, particularly gold nanoparticles (AuNPs), is being developed for a wide range of applications, including as a delivery system of peptides or nucleic acids (NA). Their use in precision medicine requires detailed engineering of NP functionalization to optimize their function and minimize off-target toxicity. Two main routes can be found in the literature for the attachment of NA strands to AuNPs: covalent binding via a thiol group or passive adsorption onto a specially adapted coating previously applied to the metallic core. In this latter case, the coating is often a positively charged polymer, as polyethylenimine, which due to its high positive charge can induce cytotoxicity. Here, we investigated an innovative strategy based on the initial coating of the particles using calix[4]arene macrocycles bearing polyethylene glycol chains as an interesting alternative to polyethylenimine for NA adsorption. Because any molecular modification of AuNPs may affect the cytotoxicity and cellular uptake, we compared the behavior of these AuNPs to that of particles obtained via a classical thiol covalent attachment in MCF-7 and GC-1 spg cell lines. We showed a high biocompatibility of both AuNPs-NA internalized in vitro. The difference in subcellular localization of both AuNPs-NA in MCF-7 cells compared to GC-1 spg cells suggests that their subcellular target is cell- and coating-dependent. This finding provides valuable insights for developing alternative NA delivery systems with a high degree of tunability.

This study explores the use of lateral flow assays (LFAs), recognized for their simplicity and ease-of-use, as a tool for characterizing nanoparticles functionalized with various biomolecules (e.g., proteins, antibodies, and nucleic acids). A half-strip model system was developed using ovalbumin (OVA) conjugated to gold nanoparticles (AuNPs). The characterization results obtained with LFAs were compared to those from traditional methods such as infrared spectroscopy and fluorescence labeling. The advantages of LFAs in characterizing such conjugated nanosystems were clearly demonstrated. The use of half-strip assays could not only confirm the presence of OVA on AuNPs but also enable the quantification of OVA bound per nanoparticle, offering a rapid and quantitative characterization method. Additionally, the assay showcased its versatility, as it was successfully applied to optimize the covalent coupling conditions of OVA on AuNPs, as well as to differentiate between covalently bound and adsorbed proteins. Furthermore, LFAs were employed to detect antibodies on functionalized nanoparticles, optimize their coupling to a newly developed organic coating, and confirm both the grafting of nucleic acids onto the surface and their pairing with complementary strands. These findings underscore the remarkable adaptability of LFAs for characterizing diverse nanoconjugates. Overall, LFAs stand out as a versatile and accessible tool for characterizing complex bioconjugated nanosystems, making them highly suitable for rapid Quality Control (QC) analysis and bioconjugation optimization.

Magnetic removal and recovery of precious metals from wastewater and complex biological media pose significant challenges mostly due to the need for efficient, selective, and stable materials. This work reports a methodology that allows these challenges to be addressed by synthesizing iron oxide nanoparticles (IONPs) coated with a covalent layer of calix[4]arene-tetracarboxylate (X4C4) capable of binding polyethylenimine (PEI) functionalities via electrostatic interactions. In contrast to citrate coating, which was previously utilized as an attachment layer for PEI, the reductive grafting of X4C4-tetra-diazonium salts onto IONPs results in a considerably more stable coating that proves to be an excellent substrate for the adsorption of PEI. This efficiently results in a synergistic interaction that significantly improves the durability of the PEI coating and maintains the particles in a dispersed state. The stability of the resulting IONPs@X4C4@PEI particles is demonstrated by their ability to withstand both acidic and alkaline conditions without significant particle aggregation or loss of magnetic properties. Moreover, these particles exhibit exceptional magnetic reusability, retaining their selectivity and recovery efficiency over multiple separation cycles. The selective affinity of IONPs@X4C4@PEI particles for gold (Au) and platinum (Pt) stems from the specific binding interactions between the complexes formed by these metals in solution and the PEI coating, enabling efficient recovery of these precious metals. This work places these IONPs at the forefront in terms of stability, reusability, and selectivity, which will undoubtedly open new avenues for environmental remediation and purification applications.