RESEARCH >> Theme: Nanomaterials for sensing applications
One of the research theme on which we are focused on is the functionalization of metal nanoparticles with organic or biological ligands in order to develop (bio)sensors or smart materials. Here is below a short summary of the 3 running projects in the EMNS Lab.
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 calixtetra-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
Collaborations: Prof. Ivan Jabin (ULB, Laboratory of Organic Chemistry)
Valkenier H., Malytskyi V., Blond P., Retout M., Mattiuzzi A., Goole J., Raussens V., Jabin I. and Bruylants G., Langmuir 33, 8253-8259 (2017).
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).
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)
Retout M., Valkenier H., Triffaux E., Doneux T., Bartik K. and Bruylants G., ACS Sensors 1(7), 929-933 (2016).
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
Development of colorimetric nanosensors for protein of medical interest using peptide functionalized gold nanoparticles
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