Quantum Dots (QDs) are fluorescent nanoparticles known for their exceptional optical properties, i.e., high fluorescence emission, photostability, narrow emission spectrum, and broad excitation wavelength. These properties make QDs an exciting choice for bioimaging applications, notably in cancer imaging. Challenges lie in their ability to specifically label targeted cells. Numerous studies have been carried out with QDs coupled to various ligands like peptides, antibodies, aptamers, etc., to achieve efficient targeting. Most studies were conducted in vitro with two-dimensional cell monolayers (n = 8902) before evolving towards more sophisticated models. Three-dimensional multicellular tumor models better recapitulate in vivo conditions by mimicking cell-to-cell and cell-matrix interactions. To date, only few studies (n = 34) were conducted in 3D in vitro models such as spheroids, whereas these models could better represent QDs behavior in tumors compared to monolayers. Thus, the purpose of this review is to present a state of the art on the studies conducted with Quantum Dots on spheroid models for imaging and phototherapy purposes.

Surgery remains the gold standard in the management of head and neck squamous cell carcinoma (HNSCC). However, the anatomical complexity of these cancers, combined with the difficulty in discriminating between healthy and cancerous tissue and the detection of microlesions, complicates tumor resection, resulting in positive surgical margins, which are associated with a poor patient prognosis. Fluorescence-guided surgery (FGS) has emerged as a promising technique in the management of HNSCC, improving tumor resection and margin assessment. FGS strategies can be roughly divided into three approaches; namely, natural tissue autofluorescence, passive delivery of fluorescent contrast agents, and active targeting. This review provides a comprehensive overview of the advances made in FGS of head and neck cancers, particularly aiming to improve surgical margin assessment. Recently, the field has shown promising results by addressing contrast agents targeted to the overexpressed epidermal growth factor receptor (EGFR), both in preclinical and clinical settings. The identification of new targets such as αVβ6 integrin, uPAR, PARP1, and so on, as well as the development of contrast agents, are key steps in the further development of FGS of head and neck cancers, making it an essential tool in precision oncology. Among these, as was demonstrated in preclinical studies, the αVβ6 integrin is emerging as a promising target due to its high and specific expression in tumor and tumor margins.

La résection chirurgicale constitue le traitement de première intention des cancers de la tête et du cou (HNSCC). La berge peropératoire est un facteur de pronostic majeur pour la survie globale des patients. Actuellement, il existe peu d’outils pour discriminer de manière fiable et en temps réel le tissu tumoral du tissu sain. La chirurgie guidée par la fluorescence (FGS) proche infrarouge (NIR) est une méthode d’imagerie utilisant le marquage fluorescent des tissus tumoraux afin de fournir une image de contraste augmentée. Le but de ces travaux est l’étude de la distribution de Quantum Dots (QDs) et d’IRDye-680, deux agents de contrastes fluorescents, couplés au peptide A20FMDV2 afin de cibler les cellules tumorales ORL au travers de l’intégrine αVβ6, surexprimée dans ces cancers. L’étude de l’accumulation et de la localisation de ces agents est réalisée sur modèle sphéroïde en monoculture et coculture (cellules cancéreuses de la langue/fibroblastes) afin de mieux représenter l’impact du microenvironnement tumoral sur la délivrance des agents de contraste. L’étude se poursuivra par le développement de nouveaux modèles sphéroïdes, mimant davantage le microenvironnement tumoral de la sphère ORL.