NANOMATERIALS FOR SENSING APPLICATIONS

#1 Controlled functionalization of gold nanoparticles

 

Gold nanoparticles (AuNP) have unique physico-chemical properties, such as their localized surface plasmon resonance (LSPR) band, and are unique candidates for development of applications in the fields of nanoimmunology, nanomedicine, and nanobiotechnology. All these potential applications however require the grafting of different functionalization moieties with controlled densities on their surface, task that is difficult to achieve rationally with the current available functionalization strategies (i.e. exploiting the affinity of thiols, amines or carboxylic acids for AuNPs). The stability and homogeneity of the grafted layer are also an issue, even when thiolated ligands are used. In close collaboration with the group of Prof. I. Jabin (ULB, LCO), we are developing a new functionalization strategy taking advantage of calix[4]tetra-diazonium salts. Once mastered, this strategy will allow us to obtain stable particles with a defined number of post-functionalizable groups.

 

 

Head: Prof. Gilles Bruylants

Co-workers/researchers: Dr Hennie Valkenier, Ir Maurice Retout

Collaborations: Prof. Ivan Jabin (ULB, Laboratory of Organic Chemistry), Prof. Claire Mangeney (Paris-Descartes), Prof. Corinne Lagrost & Dr Yann Leroux (Université de Rennes 1)

Funding: ARC

Publications:

Limits of Thiol Chemistry Revealed by Quantitative Analysis of Mixed Layers of Thiolated-PEG Ligands Grafted onto Gold Nanoparticles

Retout M., Brunetti E., Valkenier H. & Bruylants G., Journal of Colloid and Interface Science 557, 807-815 (2019).

Controlled Functionalization of Gold Nanoparticles with Mixtures of Calix[4]arenes Revealed by Infrared Spectroscopy

Valkenier H., Malytskyi V., Blond P., Retout M., Mattiuzzi A., Goole J., Raussens V., Jabin I. and Bruylants G., Langmuir 33, 8253-8259 (2017).

Extremely robust and post-functionalizable gold nanoparticles coated with calix[4]arenes via metal–carbon bonds

Troian-Gautier L., Valkenier H., Mattiuzzi A., Jabin I., Van den Brande N., Van Mele B., Hubert J., Reniers F., Bruylants G., Lagrost C. and Leroux Y., Chemical Communications 52, 10493-10496 (2016).

 

 

#2 SUBLIMUS – Becoming modern green urban alchemists: Gold and silver mining from Brussels urban sewage

 

This new project, starting in June 2019, has the objective to develop an integrated low-cost and green process to harvest the substantial quantities of gold and silver present in urban wastewater treatment plant (WWTP) sludge residues. This project proposes a novel sustainable, circular approach for producing rare and valuable purified metals from a waste stock, which is currently not valorised in the Brussels Region.

 

We are in the ULB news (22 Oct.19, in French) and various national media...

The Belgian TV show "Le grand Cactus" (Nov. 2019) was inspired by the SUBLIMUS project for one of their humorous sketches !

 

Head: Prof. Gilles Bruylants

Co-worker/researcher: Dr Carlos Moya

Collaborations: Prof. Marc Elskens, Prof. Philippe Clayes, Dr Natacha Brion (VUB), Ir Xavier Nicolay (LABiris)

Funding: INNOVIRIS - Bridge

 

 

#3 Development of a Mdm2 molecular sensor using a dual-trapping strategy with peptide aptamers

functionalized gold nanoparticles

 

The protein Mdm2 is considered to be the main negative regulator of the tumour suppressor protein p53, which is commonly called the “cellular gatekeeper for growth and division" due to its critical role in the response following a cellular stress. It has been brought to light that in more than 7% of human tumour cells Mdm2 is overexpressed (10 to 15 fold), and that this percentage increases to 20% in soft tissue tumours. The early detection of abnormal levels of Mdm2 is consequently seen as a promising diagnostic target for certain cancers. Currently, Mdm2 detection involves techniques that require expensive equipment or training skills; simple gold nanoparticle based assays would be a good alternative.

We are developing AuNP-based protein detection platform for the detection of Mdm2. The platform exploits a double recognition strategy using two sets of AuNPs, each functionalized with a different peptide aptamer. The two sets of particles are able to recognize the target protein simultaneously, via the formation of a ternary complex between the two peptides and the protein, inducing their aggregation. High selectivity is ensured by the dual-trapping mechanism.

Mdm2 was used as proof of concept of this strategy due to its strong biomedical interest, but similar peptide based dual-trapping recognition assays could be developed for other proteins. The properties of this platform (high selectivity, easy readout, efficiency of set-up, low cost) correspond perfectly with point-of- care expectations and such evolution will be envisaged. Efforts are on going to extend this system to other protein targets.

 

 

Head: Prof. Gilles Bruylants

Co-workers/researchers: Ir Maurice Retout

Collaborations: Prof. Thomas Doneux (ULB, Analytical and Interfacial Chemistry)

Funding: FER & Van Buuren (UV-Vis-NIR)

Publication:

Rapid and Selective Detection of Proteins by Dual Trapping Using Gold Nanoparticles Functionalized with Peptide Aptamers

Retout M., Valkenier H., Triffaux E., Doneux T., Bartik K. and Bruylants G., ACS Sensors 1(7), 929-933 (2016).

 

 

#4 Use of multivalent targeting to develop superselective probes for biological systems

 

The selective targeting of few specific cells among vast and extremely diverse populations is a key step in the development of effective nanocarriers for drug and gene delivery. Targets can be diseased eukaryotic cells, to be distinguished from their healthy counterparts, or pathogenic bacteria often coexisting with beneficial strains, e.g. in gut bacterial flora.

A simple approach to selective targeting consists of functionalizing the carriers with a single ligand that binds strongly to a single receptor only found on target cells. However, there are 200 different cell types in the human body and more than 10,000 different microbial species (mostly bacteria), and most of these can exist in a variety of physiological states. The fact that each cell can express many different surface receptors makes it extremely difficult to identify a receptor that is only present on the target cells.

Our goal is to take advantage of the complexity of cell membranes and design multivalent interaction schemes that are selective against a specific combination of many receptors that is likely to occur uniquely on the target. As proof-of- concept, we plan to test our strategy on synthetic model systems, in which liposomes, functionalized with DNA oligonucleotides, will mimic cells and nanoparticles, functionalized with the complementary strands, will serve as probes. We envisage exploiting the competition between “intra-probe loop complexes” and “probe-target bridges”. The free energy penalty of breaking a stable intra-probe loop complex can only be compensated if all of the ligands in the complex find their partner on the target cell, enabling to accurately select towards the simultaneous presence of multiple receptors.

 

 

Head: Prof. Gilles Bruylants

Co-workers/researchers: Dr Roberta Lanfranco

Collaborations:  Prof. Bortolo Mognetti (ULB, Physics of Complex Systems and Statistical Mechanics), Prof. Pietro Cicuta and Dr Lorenzo Di Michele (University of Cambridge, Cavendish Laboratory)

Funding: Fondation Wiener-Anspach

Publications:

Adaptable DNA interactions regulate surface triggered self assembly

Lanfranco R., Jana P. K., Bruylants G., Cicuta P., Mognetti B. M. & Di Michele L., Nanoscale (2020).

Kinetics of Nanoparticle-Membrane Adhesion Mediated by Multivalent Interactions

Lanfranco R., Jana P. K., Tunesi L., Cicuta P., Mognetti B. M., Di Michele L. and Bruylants G., Langmuir 35(6), 2002-2012 (2019).

 

 

#5 COVID-19 IMMUNOGLOBULIN DETECTION TESTS

This project is the result of a close collaboration between three ULB laboratories: EMNS, LCO and SFMB. It aims to develop two types of tests for the rapid detection of anti-SARS-CoV-2 IgG and IgM: one is based on the principle of lateral flow immunochromatography and the other on infrared spectroscopy. In the first case, the idea is to use silver nanoparticles rather than the gold nanoparticles usually used for this type of test. The researchers are betting that this modification could allow earlier detection of infection, better sensitivity of the tests and a reduction in their production cost. In the second case, the targeted Infrared biosensor should allow rapid and highly sensitive detection of IgG and IgM antibodies, as well as their quantification. This type of biosensor could be an ideal tool for high throughput analyses in hospital settings.

 

 

Promotors: Prof. Gilles Bruylants - Engineering of Molecular NanoSystems laboratory, EMNS ; Ivan Jabin - Organic Chemistry Laboratory, LCO ; Vincent Raussens - Structure and Function of Biological Membranes laboratory, SFMB.

Co-workers/researchers: Ir Maurice Retout (EMNS), Raphaël Dutour (EMNS), Bryan Gosselin (EMNS-LCO), Dr Ludovic Troian-Gautier (LCO), Pascale Blond (LCO-SFMB), Robin Bevernaegie (LCO)

Funding: ULB Special Fund COVID-19

 

Development of colorimetric nanosensors for protein of medical interest using peptide functionalized gold nanoparticles