NIR-II Semiconductor Quantum Dots and Theranostics, Semi-conducteurs de points quantiques QD NIR-II et théranostique

1. Scientific context and problematic (Contexte scientifique et problématique)

Fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) has recently emerged as a revolutionary tool in biomedical research. Compared to traditional visible and NIR-I imaging, NIR-II light experiences significantly reduced tissue scattering and minimal autofluorescence, enabling centimeter-deep tissue penetration with unprecedented spatial resolution adapted for biomedical applications.

To exploit this optical window, there is a massive demand for bright, stable, and biocompatible optical probes. Silver chalcogenide quantum dots stand out as highly promising candidates (ref 1). Unlike traditional lead- or cadmium-based quantum dots with severe toxicity concerns, silver chalcogenides are heavy-metal-free, suitable for in vivo bioimaging and clinical translation. However, a major challenge lies in low quantum efficiency due to the defects easily generated. These defects act as "traps" that capture electrons, causing energy to be lost as heat rather than emitted as NIR-II light.

To overcome these limitations, this PhD project will implement synthetic engineering for bright NIR-II quantum dots, surface engineering for biocompatibility, and preclinic validation in theranostics (Figure 1):

1. Synthesis & Photophysics: Developing and optimizing robust microwave-assisted protocols to synthesize quantum dot nanoparticles. Metal doping and shell structures will be used for brightness enhancement. The resulting products will be systematically characterized through XRD, TEM, DLS as well as photoluminescence spectroscopy. Physico-chemical characterization by capillary electrophoresis coupled to UV, fluo and other detectors will allow to synergistically optimize the synthesis in terms of impurities, size, polydispersity, etc (ref 2).
2. Surface Functionalization: As-synthesized nanoparticles are typically hydrophobic, the candidate will develop surface chemistries (ligand exchange or polymer encapsulation) to render the nanoparticles highly water-soluble, stable in biological media, and functionalized with targeting moieties (e.g., peptides or antibodies targeting cancer cells) and therapeutic photosensitizers. Physico-chemical characterization of the functionalized quantum dots will be undergone along with the studies of the nanoparticle interaction with plasmatic mimicking medium and their biotargets to optimize their biocompatibility and biodistribution properties (ref 3).
3. Bioimaging and Therapy (Theranostics): The functionalized nanoprobes will be evaluated in vitro and in vivo for toxicity and antitumoral activity. The optical probes will be used as deep-tissue NIR-II imaging contrast agents with MRI imaging as anatomic reference modality to validate preclinical performance. Furthermore, specific designed photosensitizers will be coupled on the nanoparticle surface to enable photothermal or photodynamic therapy, which can locally kill cancer cells under light irradiation (ref 4).

2. Expected outcomes (Retombées attendues)

• Development of a fast and reproducible synthetic route for NIR-II emitting nanomaterials.
• Highly bright NIR-II emitting silver chalcogenide nanoprobes with biocompatible interfaces.
• In vitro and in vivo proof-of-concepts demonstrating the superiority of these probes for multimodal imaging and therapeutic function in cancer theranostics.

3. References

1. Du, Kaimin, Liying Ma, Kun Liu, Pengpeng Lei, and Hongjie Zhang. Near-infrared-II Ag-based quantum dots for fluorescence imaging. Materials Today Bio (2025) 35, 10261
2. Wang, Zijun, Jeongmo Kim, Lilian Magermans, Francesca Corbella, Ileana Florea, Eric Larquet, Jongwook Kim, and Thierry Gacoin. Monazite LaPO₄: Eu³⁺ nanorods as strongly polarized nano-emitters. Nanoscale (2021) 13, 16968.
3. Gonzalo Ramirez-Garcia, Fanny d’Orlyé, Silvia Gutierrez-Granados, Minerva Martinez-Alfaro, Nathalie Mignet, Cyril Richard, Anne Varenne. Electrokinetic Hummel-Dreyer characterization of nanoparticle-plasma protein corona: the non-specific interactions between PEG-modified persistent luminescence nanoparticles and albumin. Colloids and Surfaces B: Biointerfaces (2017) 159, 437.
4. Sarah Boumati, Angélique Sour, Valérie Heitz, Johanne Seguin, Gautier Beitz, Yusuke Kaga, Marta Jakubaszek, Johannes Karges, Gilles Gasser, Nathalie Mignet, Bich-Thuy Doan. Three in one: in vitro and in vivo evaluation of anticancer activity of a theranostic agent that combines magnetic resonance imaging, optical bioimaging, and photodynamic therapy capabilities. ACS Applied Bio Materials (2023) 6, 4791.

ENSCP hosts Multidisciplinary research laboratories at the heart of excellence

 Chimie ParisTech hosts a research center that is active and recognized. Their fields range from the chemistry and physical chemistry of materials and surfaces, to process engineering, molecular chemistry, biochemistry, physicochemical solutions, analytical sciences and modeling.

Conscious of having to avoid any dispersion in a context of strong international competition, the school has focused its areas of activity on the sectors of energy, functional materials, in-silico design, medicinal chemistry and chemistry for the living. Chimie ParisTech also aims to highlight the strong technological aspect of its activities, which represents a major asset for education.

The school has around one hundred permanent researchers and teacher researchers across its 3 laboratories, about a third of which are members of the CNRS.

The ICleHS is one of the 3 laboratories. i-CLeHS laboratory is composed by 5 research teams with complementary know-how and expertise developing innovative concepts and research in Chemistry with applications in Life and Health Sciences. Their skills and expertise include molecular, medicinal, inorganic, physical and theoretical chemistry, as well as imaging, diagnostic and analytical systems, for the development of applications ranging from biology and environment till health issues. 

Actually, the SEISAD Team develops projects aimed at elaborating processes and tools for the early detection of pathological signals using chemical and analytical methodologies. The main prospections are related to: (i) new methodologies of synthesis of nanoparticles, functionalisation, hydrogels and active compounds; (ii) electrochemical sensors for biological systems and for screening biological markers, molecular materials for electroanalysis and electrocatalysis, microelectrochemical patterning of surfaces using scanning electrochemical microscopy,  ; (iii) preparation of targeted optical and MR imaging agents, development of molecular magnetic resonance imaging MRI methods & functional imaging methods for the characterization and therapeutic follow-up of cancer in preclinics and (iv) characterization of new nano-supports and selective objects : peptide nanotubes, aptamers, nanobodies, design and characterization of original biocompatible nano-objects and quantitative characterization of their non-covalent interactions, development of miniaturized total analysis systems wuith capillary electrophoresis for applications ranging from environmental control to in-vitro medical diagnosis.

• Education: Master’s degree (or equivalent engineering degree) related to Chemistry, Materials Science, Biomedical Engineering or Bioimaging.
• Hard Skills: Strong background in colloidal chemistry and synthesis. Previous experience with nanoparticle synthesis, optical spectroscopy (UV-Vis, photoluminescence), surface functionalization, biomedicine, structural and chemical characterization (TEM, XRD, analytical methods) is highly desirable.
• Interests: A strong motivation to work at the interface of chemistry and biology, in multidisciplinary domains. While biological experiments will be done in collaboration, the candidate must be eager to learn cell culture, in vitro assay techniques, analytical methods, and bioimaging.
• Soft Skills: Scientific rigor, critical thinking, autonomy, and good communication skills in English (written and spoken).