Elsa Cassette

Cadmium-Free CuInS2/ZnS Quantum Dots for Sentinel Lymph Node Imaging with Reduced Toxicity

Semiconductor quantum dots (QDs) could significantly impact the performance of biomedical near-infrared (NIR) imaging by providing fluorescent probes that are brighter and more photostable than conventional organic dyes. However, the toxicity of the components of NIR emitting II-VI and IV-VI QDs that have been made so far (Cd, Hg, Te, Pb, etc.) has remained a major obstacle to the clinical use of QDs. Here, we present the synthesis of CuInS(2)/ZnS core/shell QDs emitting in the NIR ( approximately 800 nm) with good quantum yield and stability even after transfer into water. We demonstrate the potential of these QDs by imaging two regional lymph nodes (LNs) in vivo in mice. We then compare the inflammatory response of the axillary LN induced by different doses of CuInS(2)/ZnS and CdTeSe/CdZnS QDs and show a clear difference in acute local toxicity, the onset of inflammation only occurring at a 10 times more concentrated dose for CuInS(2)/ZnS QDs than for their Cd-containing counterparts.

Design of new quantum dot materials for deep tissue infrared imaging

Near infrared fluorescence offers several advantages for tissue and in vivo imaging thanks to deeper photon penetration. In this article, we review a promising class of near infrared emitting probes based on semiconductor quantum dots (QDs), which have the potential to considerably improve in vivo fluorescence imaging thanks to their high brightness and stability. We discuss in particular the different criteria to optimize the design of near infrared QDs. We present the recent developments in the synthesis of novel QD materials and their different in vivo imaging applications, including lymph node localization, vasculature imaging, tumor localization, as well as cell tracking and QD-based multimodal probes.

Visualisation of sentinel lymph node with indium-based near infrared emitting Quantum Dots in a murine metastatic breast cancer model.

Due to its non-invasiveness, high temporal resolution and lower cost, fluorescence imaging is an interesting alternative to the current method (blue dye and radiocolloid) of sentinel lymph node (SLN) mapping in breast cancer. Near-infrared (NIR) emitting cadmium-based Quantum Dots (QDs) could be used for this purpose; however, their wide application is limited because of the toxicity of heavy metals composing the core. Our recent work demonstrated that indium-based QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based counterparts. In the present study we confirmed the weak toxicity of CuInS2/ZnS QDs in different in vitro models. Further in vivo studies in healthy mice showed that In-based QDs could be visualised in SLN in a few minutes after administration with a progressive increase in fluorescence until 8 h. The quantity of indium was assessed in selected organs and tissues by inductively coupled plasma – mass spectroscopy (ICP-MS) as a function of post-injection time. QD levels decrease rapidly at the injection point in the first hours after administration with a parallel increase in the lymph nodes and to a lesser extent in the liver and spleen. In addition, we observed that 3.5% of the injected indium dose was excreted in faeces in the first 4 days, with only trace quantities in the urine. Metastatic spread to the lymph nodes may hamper its visualisation. Therefore, we further performed non-invasive fluorescence measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed by immunohistology and molecular techniques and revealed the utmost metastatic invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN tracer.

Compact tridentate ligands for enhanced aqueous stability of quantum dots and in vivo imaging

We describe here a simple and versatile route for the preparation of a tridentate ligand that not only provides stable interactions with colloidal semiconductor nanocrystals (quantum dots, QDs) but also makes them water soluble. The designed ligand incorporates a biocompatible solubilizing polyethylene glycol (PEG) chain connected to a tridentate thiol motif with improved affinity towards the QDs surface. Stability experiments revealed better resistance to various drastic conditions compared to classical dihydrolipoic-based ligands. The enhanced stability of the assembly also enabled in vivo imaging experiments using near infrared-emitting QDs.

On the characterization of the surface chemistry of quantum dots.

The interaction of ligands with the surface of quantum dots (QD) was studied using tritiated oleic acid as an ultrasensitive reporter. The use of labeled oleic acid not only permitted to quantify the number of ligands attached to the surface of QDs of various sizes but also enabled the investigation of the relative affinity of different ligand types for the nanocrystals surface.