2 ans à partir du 01/09/2022

Postdoctoral position at the interface of physical-chemistry/photobiology for the development of anticancer phototheranostic nanoparticules

We offer a two-years postdoc position to work on the chemical to in vivo development of ICG-based phototheranostic nanoparticles as mentioned above. Within the frame of this project, both the physico-chemical (nanoparticles formulation, chemical and photophysical analysis) and the biological (in cellulo and in vivo phototherapeutic activities evaluation) aspects will be investigated. A good expertise in photochemistry/photobiology will be required and valued by combination with high expertise in chemistry, physico-chemical engineering, photophysics and cellular/small animal biological studies of L2CM and CRAN. As a postdoctoral researcher, you will be attached to both laboratories, which are located in Vandoeuvre-les-Nancy, France. You will be supervised by Y. Bernhard at L2CM and H-P Lassalle at CRAN.

• Research topic of the postdoc:

Photobiology, physical-chemistry, organic nanoparticles, photophysical characterization, biological chemistry, cellular biology, nanotheranostics, photothermal therapy, fluorescence imaging, photoacoustic imaging.
Context and research objectives:
Over the last decade, photothermal therapy (PTT) have attracted increasing attention as a potential alternative to other classical therapeutic approaches. It involves molecules or nanoparticles absorbing photons upon NIR irradiation and generating heat through non-radiative relaxation pathways. To help the clinical translation of PTT, which is currently limited to a few early phase pilot trials, highly challenging research aspects concern the development of theranostic nanoparticles that provide efficient photothermal therapeutic effect in combination with comprehensive image-guiding strategy by fluorescence/photoacoustic imaging (PAI).
Indocyanine Green (ICG) is so far the only FDA-approved dye for fluorescent application, and therefore stays on the frontline for fast pre-clinical and clinical PTT evaluation. Unfortunately, at the molecular scale it exhibits limited PTT efficiency, accumulation at tumor site, and bio/photo-stability. Therefore, its formulation in supramolecular assemblies is of particular significance to improve its pharmacokinetics and PTT performances. In this context, our group is exploiting the physico-chemical engineering of ICG into so-called J-type aggregates (i.e. Indocyanine green J-aggregates, IJA), which demonstrates better PTT efficiency and response as contrast agent in PAI, as compared with ICG. However, because IJA quickly disassemble in complex biological media, research efforts are dedicated to the stabilization of IJA by appropriate formulation. In continuity with our ongoing research work, the project aims at 1) improve the comprehension of IJA chemical nature and structure at both molecular and self-assembled scale; 2) develop outperforming innovative IJA-based nanoparticles; 3) engineers these nanoparticles to incorporate a second fluorophore (e.g. commercial cyanines) for additional imaging outcomes, to targets in vivo intelligent fluorescent organic nanoparticles for dual image (PTT/PAI) -guided PTT strategy.


Mission and specific responsibilities:

You will be responsible and/or participate to the following tasks:

• Study of the structure and nature of IJA and its degradation products at molecular and self-assembled scale using chemical analysis technics (HPLC, NMR, Mass spectrometry).

• Preparation and characterization of fully organic IJA-based nanoparticles using physico-chemical engineering (e.g. surfactant-based nanoparticles, polymeric micelles, liposomes, nanoparticles constructed by electrostatic interactions) – Bringing forward ambitious and realistic design of new theranostic nanoparticles

• Assessment of photophysical properties of nanoparticles by photophysical technics (spectroscopy, fluorimetry, photothermal production setup)

• Investigation of photothermal activity, (photo)chemical stability in biological environments, evaluation of dark/photo toxicities, cellular uptakes/localization (FaDU cancer cell model and 3D cell models).

• In vivo investigation on mouse models bearing head and neck tumors (in vivo/ex vivo distribution, photothermal treatment, imaging using bimodal fluorescence/photoacoustic imaging equipment) – A formation for in vivo working with small animal models will be provided within the postdoc.

• Participation in the supervision of PhDs, engineers, and trainees – restoring the results, communication at international conferences, participation in writing of manuscripts.


• Candidate profile and application form:
You should hold a PhD in photobiology with prior experience in cell biology and at the interface with physical-chemistry/photophysics. Additional experience in formulation/nanoparticle synthesis and characterization, fluorophore synthesis and characterization (spectrofluorimetry, HPLC) or in vivo fluorescence/photoacoustic imaging would be appreciated. Creativity, autonomy and strong reliability are highly required, together with strong interest in multidisciplinary approach. This project will give great opportunities to develop/extend competences in photophysics, physical chemistry, cell biology and associated characterization techniques with cutting-edge equipment. You are expected to be highly motivated and possess great team spirit to take advantages to work in a leading research environment and potentially make breakthrough innovation in cancer treatments. All applicants must be able to communicate fluently in English. Applications should be sent to Yann Bernhard (yann.bernhard@univ-lorraine.fr) and Henri-Pierre Lassalle (henri-pierre.lassalle@univ-lorraine.fr ). It should include a detailed CV and a cover letter highlighting how you meet the criteria.

Supervisors of the postdoc:
Yann Bernhard (MCF, team MolSyBiO, L2CM) and Henri-Pierre Lassalle (MCF, team BioSIS, CRAN)

Dr. Yann Bernhard - Contacter
1) Laboratoire Lorrain de Chimie Moléculaire (L2CM, UMR 7053), http://www.l2cm.univ-lorraine.fr/l2cm/, Boulevard des Aiguillettes B.P. 70239 - 54506 Vandoeuvre les Nancy Cedex France
2) Centre de Recherche en Automatique de Nancy (CRAN, UMR 7039, http://www.cran.univ-lorraine.fr/, Campus Sciences BP 70239 54506, Vandoeuvre-lès-Nancy

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5 ans

Chaire de professeur junior

Chaire de professeur junior

Profil recherche : Métaux abondants pour la synthèse organique asymétrique.

Composante d'enseignement : UFR Sciences Fondamentales et Appliquées (SciFA).

Les candidatures doivent être déposées en version numérique sur Galaxie (module FIDIS (fil de l'eau)*) selon le calendrier disponible sur le site de L'Université de Lorraine. Pour plus d'information, consultez la fiche de poste.

5-6 mois début janvier 2023

Stage M2 : Organic synthesis and encapsulation of Aggregation Induced Emission (AIE) dyes for phototheranostic applications

Context: Light-assisted imaging, therapeutic and merged (theranostic) approaches are ever-expanding in medicine. Photothermal therapy (PTT) coupled to photoacoustic and fluorescence imaging, which relies on heat/ultrasound production and fluorescence emission upon light irradiation, stand on the frontline of theranostic approaches under development. In addition, the possibility of bringing energy to the system by biphotonic excitation opens way to access the near infrared window, which is more suitable for in vivo applications. In this domain, there is a need of novel agents which could efficiently integrate these multiple features in one structure. Fluorophores combining properties of aggregation-induced emission (AIE) and two-photon absorption are promising candidates.

Research objectives: The aim of this study will concern the synthesis of dyes from the families of quinoline-malonitrile (QM), dicyanomethylene-2H-chromene (DCM) and benzo-bis-thiadiazole (BBTD). Structural modulations of the organic scaffold via modification of the substituents will be conducted to optimize the structure and achieve AIE and two-photon absorbing properties. The work will be mostly dedicated to the multistep organic synthesis of already known and novel compounds.