The outgrowth of biofilms is accompanied by a severe resistance towards detergents and antibiotics. The COPPERTREE project aims at developping an alternative strategy against biofilms to the ones currently in use. The goal is to treat surfaces with a coating that is expected to offer a passive proetction (antiadhesive) and an active protection (biocidal effect).
Bacterial colonies grow on many surfaces. These biofilms are present in evaporation towers of nuclear power plants or on the submerged part of ship hulls. They are sometimes resistant to conventional antibacterial treatments, and can be the cause of serious infections when developing on implants or prostheses used in medicine. <br />The COPPERTREE project aims at devleopping coatings made of copper nanoparticle in a dendrimer matrix (molecular tree). These coatings could have a anti-adhesion-like passive properties and an active effect (bacteriostatic or bactericidal effect) to kill organisms which deposit on it. After validation on model surfaces, this technology could be transferred to plastic, glass-based materials or metal, with possible applicatioons applications for processing large industrial surfaces or biomedical devices surfaces. <br />
The methodology is based on the obtaining of a stable deposition of copper nanoparticles in a dendrimer matrix with two complementary effects. These effects will be related to the properties of dendrimers, also known as molecular trees, which show good adhesion properties thanks to their multivalent surface and good stabilization properties towards nanoparticles owing to their multivalent surface and their hyperbranched structure. The effect of the nanoparticles will also be measured, depending on their size and on their composition. The hybrid interface is expected to meet the requirements of stability thanks the multivalency of dendrimers. The core of the coating will be an multilayer or a heterogeneous matrix of copper nanoparticles and dendrimers phosphorus stabilizing these nanoparticles. Original Janus-type dendrimeric systems comprising a PEG face intended to prevent the adhesion of colonizing microorganisms and a «multi-phosphonates« face for the grafting on metal surface. The first treatments will be applied on wafer-type models of surfaces, on which the chemical composition and surface roughness are perfectly controlled.
The COPPERTREE project allowed the development of new methods of synthesis of hyperbranched macromolecules with polyethylene glycol functions (or PEG, antiadhesive against microorganisms) and phosphonates functions (adhesives and stabilizing towards nanoparticles). Some of these molecules have been grafted onto finely divided solids (silica, titanium oxide) and hosted the synthesis of silver nanoparticles. These nanoscale assemblies are well-controlled and present good bactericidal properties. The ligands/surface interactions within certain copper nanoparticles and their influence on the oxidation processes of these nanoparticles are better understood, and new antibacterial coatings have been developed.
The project has lead to the publication of 6 scientific articles, 5 communications sin international congresses and 2 communications in national congresses.
1. Low generation PEGylated phosphorus-containing dendrons with phosphonate anchors.
C. Barrière, V. Latour, P. Fau, A.-M. Caminade, C.-O. Turrin
Tet. Lett. 2012, 53, 1908-1911
2. Application of the Kabachnik-Fields and Moedritzer-Irani procedures for the preparation of PEG-terminated amino-bis(methylene phosphonates) and amino-bis(methylene-phosphonic acids).
C.-O. Turrin, A. Hameau, A.-M. Caminade.
Synthesis 2012, 44, 1628-1630
3. PPH dendrimers grafted on silica nanoparticles: surface chemistry, characterization and silver colloids hosting and bactericide activity; A. Hameau, V. Collière, C.Roques, P. Fau, A.-M. Caminade, C.-O. Turrin, RSC Advances, 2013, 3, 19015-19026
4. Deciphering Ligands’ Interaction with Cu and Cu2O Nanocrystals Surface by NMR Solution Tools
A. Glaria, J. Cure, K. Piettre, Y. Coppel, C.O. Turrin, B. Chaudret, P. Fau
Chem. Eur. J. 2014, 21, 1169-1178
5. Theoretical and experimental characterization of amino-PEG-phosphonate-terminated PolyPhosphor-¬Hydrazone dendrimers. Influence of size and PEG capping on cytotoxicity profiles
A. Hameau, S. Fruchon, C. Bijani, A. Barducci, M. Blanzat, R. Poupot, G.M. Pavan, A.M. Caminade, C.O.Turrin
J. Polym. Sci. Part A. Polym. Chem. 2015, 53, 761-774
6. Thiophosphate/phosphonate-containing cross-linked PEGs and their use for the stabilization of silver nanoparticles
A. Hameau, A. Glaria, V. Collières, A.M. Caminade, C.O. Turrin
Heteroatom. Chem. 2015, 4, 299-306
The superior bactericidal activity of Cu nanoparticles compared to bulk Cu has been demonstrated, and is related to the ability of the latter to release cupric (Cu2+) ions. Thin films containing Cu nanoparticles should present bacteriostatic and even bactericidal properties that would be of great interest for surface treatments and anti-biofilm purposes with a copper loading in the 1% range (cf Langmuir 2008, 24, p2430). This 1% payload should be compared to the minimum 50% toxic payload of antifouling paintings that are used to cover boats and vessels, which are fully removed to the sea within a couple of years. On the other hand, the anti-adhesive properties of polyethyleneglycol chains (PEG) towards micro-organisms has also been demonstrated and has led to the development of "furtive" drug delivery systems and other biocompatibe materials. Thus, the use of copper nanoparticles entraped in a stabilizing polymeric matrix with a toping made of PEG chains is highly relevant for the deposition of thin film having anti-biofilm properties based on a bactericidal/anti-adhesion synergical effect. In this approach, the Cu NPs are considered as a Cu2+ (biocide) reservoir. To improve the efficiency of the concept, the stability of the Cu nanoparticles entrapped in the micronic coating must be controled in order to release the correct amount of Cu2+. To achieve this goal we propose to use macromolecular scaffolds specially designed for this purposes, namely dendrimeric systems, according to a Layer by Layer (LbL) deposition strategy (alternating with Cu NPs). The LbL technique is actually one of the most efficient and readily accessible method to produce highly adherent functionalized thin films. In addition it has been validated in our group for the preparation of multilayer thin film comprising phosphorus dendrimers and gold colloids (Caminade et al. J. Mater. Chem. 2009, p2006). The adaptable dendrimeric platform of the project are based on phosphorus containing dendrimer equipped mainly with phosphonate (or phosphonic acid) surface functions. Actually, our preliminary results have shown that these dendrimers strongly adhere to several surfaces and that they are also very efficient to stabilize thin films containing Cu NPs.
The hybrid interface between the support and the coating will be conceived to maximize the stability of the deposited multilayers, by using a technique which as already proved its efficiency for the industrial production of dendrimer-based biochips. The interface between the coating and the external media will be designed with Janus-type dendrons having a Cu-sticking face (phosphonate termiantions) and anti-adhesive (bacteria repellent) PEG tails on the other face.
The biological properties of such films are unknown, and the literature on anti-microbial activity of cupric ions excreted by colloidal systems of metallic copper is scarce. In this context, the COPPERTREE project will explore the possibilities offered by this original and innovating hybird system based on the following key points: 1/ The strong adhesion of the film thanks to the multivalent architecture; 2/ The stabilization of the nanoparticles that can be controled by the dendrimer surface and interior; 3/ The intrinsic antimicrobial activity of Cu NPs; 4/ The anti-adhesion properties of the final system thanks to the PEG chains of the Janus-like dendron toping.
Monsieur Cédric-Olivier TURRIN (CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE MIDI-PYRENEES) – email@example.com
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
LCC CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE MIDI-PYRENEES
LGC (UPS) UNIVERSITE TOULOUSE III [PAUL SABATIER]
LCC CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE MIDI-PYRENEES
Help of the ANR 461,730 euros
Beginning and duration of the scientific project: October 2011 - 42 Months