Ann Oncol 2019; (doi: 10.1093/annonc/mdz124 )

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.

Objective To evaluate the recurrence rate after a single treatment of vulvar intraepithelial neoplasia (VIN) with CO₂ laser vaporization. Materials and Methods Fifty women with usual-type or differentiated VIN (grades 2 and 3) treated with CO₂ laser vaporization or surgery excision (cold knife or CO₂ laser) were retrospectively evaluated. Results Of the 50 patients, 41 (82.0%) had usual-type VIN and 9 (18.0%) had differentiated VIN. Moreover, 24 (48.0%) were treated with surgery excision and 26 (52.0%) underwent CO₂ laser vaporization. Laser-treated patients were significantly younger (p < .01) with more multifocal (p < .05) and multicentric lesions (p < .01) than in the surgery group. Recurrence-free survival (RFS) rates at 1 year were 91.0% for the surgery and 65.2% for the laser vaporization groups (p < .01). At 5 years, RFS rates were unchanged for the surgery group and dropped to 51.3% (p < .01) for the laser group. On the univariate analysis, current smoker (p = .03), multicentric VIN (p = .02), and laser vaporization treatment (p < .01) had a statistically significant impact on RFS. One patient progressed to invasive cancer (2%). Conclusions The recurrence rate after CO₂ laser vaporization requires regular, close, and extended monitoring.

The efficient intraoperative identification of cancers requires the development of the bright, minimally-toxic, tumor-specific near-infrared (NIR) probes as contrast agents. Luminescent semiconductor quantum dots (QDs) offer several unique advantages for in vivo cellular imaging by providing bright and photostable fluorescent probes. Here, we present the synthesis of ZnCuInSe/ZnS core/shell QDs emitting in NIR (~750 nm) conjugated to NAVPNLRGDLQVLAQKVART (A20FMDV2) peptide for targeting α_vβ₆ integrin-rich head and neck squamous cell carcinoma (HNSCC). Integrin α_vβ₆ is usually not detectable in nonpathological tissues, but is highly upregulated in HNSCC. QD-A20 showed α_vβ₆ integrin-specific binding in two-dimension (2D) monolayer and three-dimension (3D) spheroid in vitro HNSCC models. QD-A20 exhibit limited penetration (ca. 50 µm) in stroma-rich 3D spheroids. Finally, we demonstrated the potential of these QDs by time-gated fluorescence imaging of stroma-rich 3D spheroids placed onto mm-thick tissue slices to mimic imaging conditions in tissues. Overall, QD-A20 could be considered as highly promising nanoprobes for NIR bioimaging and imaging-guided surgery.

This contribution presents the development of an optical spectroscopy device, called SpectroLive, that allows spatially-resolved multiply-excited autofluorescence and diffuse reflectance measurements. Besides describing the device, this study aims at presenting the metrological and safety regulation validations performed towards its aimed application to skin carcinoma in vivo diagnosis. This device is made of six light sources and four spectrometers for detection of the back-scattered intensity spectra collected through an optical probe (made of several optical fibers) featuring four source-to-detector separations (from 400 to 1000 µm). In order to be allowed by the French authorities to be evaluated in clinics, the SpectroLive device was successfully checked for electromagnetic compatibility and electrical and photobiological safety. In order to process spectra, spectral correction and metrological calibration were implemented in the post-processing software. Finally, we characterized the device’s sensitivity to autofluorescence detection: excitation light irradiance at the optical probe tip in contact with skin surface ranges from 2 to 11 W/m², depending on the light source. Such irradiances combined to sensitive detectors allow the device to acquire a full spectroscopic sequence within 6 s which is a short enough duration to be compatible with optical-guided surgery. All these results about sensitivity and safety make the SpectroLive device mature enough to be evaluated through a clinical trial that aims at evaluating its diagnostic accuracy for skin carcinoma diagnosis.