Ph. D. Project
Functionalization of Quantum Dots in the near infrared and quantification of fluorescence on cell models: application to fluorescence-guided surgery of ENT cancers
2021/09/02 - 2024/09/01
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Surgical resection remains the first-line treatment for
these cancers. Intraoperative margin is considered an important prognostic factor for overall survival. Currently, there are few tools to reliably discriminate
tumor tissue from healthy ones in real time. Intraoperative surgery using fluorescence imaging (FGS) in the near infrared (NIR) is an imaging method that
uses fluorescent labeling of tumor tissue to provide enhanced contrast imaging. The FluORL project aims to address both fundamental issues (in biology and
image processing) and applied issues (in biomedical optics), with the clinical goal of optimizing the use of fluorescence imaging for surgical resection of
ENT cancers. The multidisciplinary FluORL project is organized in three tasks. The first task concerns the work that will be carried out in biology: our team,
in collaboration with chemists from ESPCI (Dr T Pons), is studying the use of Indium-based Quantum dots (QDs)-NIR. These low toxicity QDs exceed the
optical properties of chemical fluorophores in terms of brightness and photo-stability. Improving the specificity of the fluorophores by chemical coupling to
ligands will result in better contrast; 95% of HNSCC cancers overexpressing avb6 integrin receptors, we propose avb6 integrin QDs for this study. We will
use 3D cells in mono- and heteroculture (cancer cells/cancer-associated fibroblasts, CAFs) because CAFs are present in large quantities in HNSCC cancers
and can represent a physical barrier for QD penetration. We will study the accumulation, penetration and distribution of QDs- NIR in mono- and co culture.
Subsequently, from patient ENT tumors, we will develop a 3D organoid model that maintains the architecture and cellular composition of the ENT tumors.
Once the model has been optimized, we will test the accumulation, distribution and selectivity of QDs-NIR. The two other tasks of the FluORL project,
which concern image processing and biomedical optics, aim to provide the surgeon with visualization comfort by producing from video-endoscopic
sequences panoramic images of the oral mucosa on which the fluorescence emission will be quantified. Indeed, endoscopic visualization of the oral mucosa
only allows the observation of about 2 cm of oral mucosa. As cancerous lesions are often multifocal, the panoramic image will allow to produce an image
allowing the bimodal visualization of at least 10 cm of oral mucosa, providing the surgeon with a global vision of his surgical field. This work will be
carried out primarily on endoscopic videos acquired from patients (having given their prior informed consent), those videos for which indocyanine green
will be the used. The task 3 will also be applied to the quantification of the fluorescence of QDs in organoid models,
once the latters will be developed in the first task of the FluORL project, dedicated to biology.
This is collaborative multidisciplinary project regrouping scientific expertise of our colleagues from IRTB group (Pr W Blondel; Dr M Amoureaux),
chemists from ESPCI, Paris (Dr T Pons) and making a part of international project PHC Kolmogorov with the group of Prof V Loschenov (Institute of
General Physics, Moscow, Russia).
The objective of the thesis will be to advance knowledge in tasks 1 (cell biology) and 3 (biomedical optics) of the FluORL project at the interface with the
researchers involved in task 2 (image processing). The future PhD student will thus be in charge of the development of cellular models for the
characterization of the distribution of QDs-NIR and the quantification of fluorescence within these models.
Biology, Signals and Systems in Cancer and Neuroscience