Intitulé du sujet: Dual-Action Nanohybrid Materials for Photothermal Therapy and Targeted Drug Delivery
Sujet
Codirection:
Nombre de mois: 48 mois
Ecole Doctorale: ED 388 - Chimie physique et Chimie analytique de Paris centre
Unité de recherche et équipe:
Laboratoire ITODYS UMR 7086, Equipe Sustainable Materials for Life (SML) - département D3
Coordonnées de l’équipe:
Responsable Equipe Sustainable Materials for Life - département D3 - Laboratoire ITODYS
Pr. Miryana HEMADI
15, rue Jean-Antoine de Baïf
75013 - Paris
Email: hemadi@u-paris.fr
Phone: +33157278839
Secteur: Sciences Physiques et Ingénierie / Physical sciences and Engineering
Langue attendue: Anglais
Niveau de langue attendu: B1
Description
Description du sujet:
The emergence of multidrug-resistant bacteria and the persistence of biofilms pose significant challenges in combating bacterial infections [1]. Biofilms are involved in a wide variety of microbial infections in the body, such as skin wounds, urinary tract infections, catheter infections and formation of dental plaque, and cause more than 80% of infections in humans. While traditional antibiotic treatments are effective on planktonic bacteria, they are much less effective on biofilms. Studies have been carried out to understand the molecular mechanisms allowing the formation and dispersion of biofilms in order to better control pharmaceutical and technological developments aimed at preventing or eradicating their formation. The SML team has developed know-how on hybrid nanomaterials for biomedical and environmental applications [2-10].
Our objective in this PhD thesis is to develop a new strategy based on magnetic actuation and photothermia to eradicate bacterial biofilms. To this end, light-activated nanoparticles (NPs) will, by thermal therapy, be used to boost antibiotic treatments. The different therapeutic strategies based on NPs used so far show that the diffusion of nanoparticles in a biofilm strongly limits the effectiveness of this technique, but the superparamagnetic NPs we plan to use here can be manoeuvred by a magnetic field to displace them within the biofilm matrix.
To validate the proof of concept, biological studies will be performed to determine the Minimal Inhibitory Concentration (MIC) and the bactericidal activity of the nnaohybrids on Gram-positive and Gram-negative bacteria in the planktonic and biofilm states.
Objectives:
The main objectives of the thesis are as follows:
- a) Elaboration of hybrid nanomaterials
Different types of nanoparticles will be used: iron oxide NPs and carbon dots (CDs). These different types of NPs are chosen for their magnetic and optical properties.
Photosensitizers (PSs; synthetic or commercially available molecules: derivatives of cyanine,
phthalocyanine, hematoporphyrin) with active molecules (inhibitors, bactericides, enzymes).
will complete these assemblies. PSs and active molecules will be incorporated either by
electrostatic interaction or via a covalent bond (Diels-Alder, click chemistry, esterification, etc.).
- b) Study of physicochemical properties
The physicochemical properties of the NPs alone and of the different nanohybrids/assemblies
will be studied in order to highlight the synergy, if present, between the different building blocks; below are some examples:
Photothermia: Measurement of the temperature rise after laser irradiation of NPs and nanohybrids.
Photodynamics: After excitation of PSs with a laser, the transfer of energy to oxygen causes the formation of reactive oxygen species, notably singlet oxygen.
Colloidal stability: Nanohybrids/assemblies must be well dispersed in the biofilms and must not aggregate in the medium.
Magnetic properties: Saturation magnetization will be measured to ensure that assemblies retain their magnetic properties.
Optical properties: Measurement of fluorescence absorption and emission spectra.
Internalization: Monitored by benchtop confocal microscopy.
- c) Applications of hybrid nanomaterials on bacterial biofilms
Selected nanohybrids will be tested on biofilms of different bacterial species and strains. This is an important step to test the synergy of the assemblies.
The perspective of this thesis is very promising, with avenues of research exploring the combination of several stimuli. For example, the incorporation of stimulable nanomaterials into gels or dressings could offer an effective solution to eradicate bacterial biofilms in different contexts. Additionally, smart dressings can evolve and combine laser irradiation with the application of a magnetic field to eradicate bacterial biofilms present in infected wounds.
Methodology:
The objectives set in the thesis will use classic nanoparticle synthesis and characterization methods (ATG, XPS, SEM, SERS, VSM, TEM, FTIR, DLS, confocal microscopy, etc.) available within the ITODYS laboratory and other platforms at the Faculty of Sciences.
Compétences requises:
Candidate should be interested in the synthesis and functionalization of nanoparticles. A good knowledge of physicochemistry, and materials chemistry is required.
Références bibliographiques:
Recent Bibliography:
[1] Recent advances in nanotechnology for eradicating bacterial biofilm. Sahli C, Moya SE, Lomas JS, Gravier-Pelletier C, Briandet R, Hémadi M. Theranostics, 2022, 12, 2383-2405 [Link]
[2] Eradication of planktonic bacteria by shape-tailored gold nanoparticle photothermia. Peng Z, Royon L, Luo Y, Decorse P, Gam Derouich S, Bosco M, Gravier-Pelletier C, Briandet R, Lomas JS, Mangeney C, Hémadi M. Materials Advances. 2024, 5, 8524-8533 [Link]
[3] Dual therapy for the eradication of bacterial biofilms: Iron oxide nanoparticles and carbon dots as magnetic actuator and photothermal agents. Sahli C, Deschamps J, Royon L, Lomas JS, Briandet R, Hémadi M. Materials Today Chemistry. 2024, 35, 101920 [Link]
[4] Iron oxide nanoparticles (Fe3O4, d-Fe2O3 and FeO) as photothermal heat mediators in the first, second and third biological windows. Roca AG, Lopez-Barbera JF, Lafuente A., Özel F, Fantechi E, Muro-Cruces J, Hémadi M, Sepulveda B, Nogues J. Physics Reports, 2023, 1043, 1-35 [Link]
[5] Functionalized maghemite nanoparticles for enhanced adsorption of uranium from simulated wastewater and magnetic harvesting. Xiao Y, Helal AS, Mazario E, Mayoral A, Chevillot-Biraud A, Decorse P, Losno R, Maurel F, Ammar S, Lomas JS, Hémadi M. Environmental Research, 2022, 216, 114569 [Link]
[6] TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia. Belkahla H, Mazarío E, Lomas JS, Gharbi T, Ammar S, Micheau O, Wilhelm C, and Hémadi M. Theranostics, 2019, 9, 5924-5936 [Link]
[7] Grafting TRAIL through either amino or carboxylic groups onto maghemite nanoparticles: Influence on pro-apoptotic efficiency. Belkahla H, Constantinescu A.A, Gharbi T, Barbault F, Chevillot-Biraud A, Decorse P, Micheau O, Hémadi M, Ammar S. Nanomaterials, 2021, 11, 502 [Link]
[8] Carbon dots, a powerful non-toxic support for bioimaging by fluorescence nanoscopy and eradication of bacteria by photothermia. Belkahla H, Boudjemaa R, Caorsi V, Pineau D, Curcio A, Lomas JS, Decorse P, Chevillot-Biraud A, Wilhelm C, Randriamahazaka H, and Hémadi, M. Nanoscale Advances, 2019 [Link]
[9] Magnetic nanoparticles in regenerative medicine: what of their fate and impact in stem cells? Van de Walle A, Pereza JE, Abou-Hassan A, Hémadi M, Luciania N, and Wilhelm C. Materials Today Nano, 2020, 11, 1000084 [Link]
[10] Highly efficient non-enzymatic electrochemical glucose sensor based on carbon nanotubes functionalized by molybdenum disulfide and decorated with nickel nanoparticles (GCE/CNT/MoS2/NiNPs). Fall B, Sall DD, Hémadi M, Diaw AKD, Fall M, Randriamahazaka H, Thomas S. Sensors and Actuators Reports, 2022, 5, 100136 [Link]
