Imaging techniques used in the clinic include magnetic resonance imaging, computed tomography, and positron emission tomography. They require cumbersome and expensive setups, and some of them employ dangerous ionizing radiation. Fluorescence imaging (FI) is instead a non-invasive, inexpensive imaging technique that uses lower-energy radiation. It also boasts fast acquisition times, enabling real-time monitoring of biological processes within tissues of interests. As appealing as FI might sound, its application in the clinical context is a far reality. To obtain an image via FI, a contrast agent is required that accumulates at the site of interest and emit light when illuminated with light of proper energy. In this vein, luminescent nanoparticles are arguably the most promising candidates. Indeed, being thousand of times smaller than a single cell, they can target malignant tissues that are below the minimum size detectable with other diagnostic tools, hence allowing for treatments to be initiated early on. To be used in FI, luminescent nanoparticles should absorb and emit photons in the near-infrared (NIR) spectral range (750-1800 nm), because biological tissues are less impervious to light in this range (Figure 1). Unfortunately, there is a lack of nanoparticles that absorb and emit NIR photons efficiently enough to make FI a credible alternative to the above-mentioned imaging techniques. The development of FI contrast agents in the form of NIR luminescent nanoparticles with superior performance is therefore an urgent matter and of immense projected impact on future society, contributing at least on two fronts to its prosperity:
- reduction of direct and indirect costs sustained by the health system - stemming from the timely detection of diseases and use of less expensive equipment;
- increased well-being of the patients - thanks to the minimal discomfort sustained by the patient during the imaging process and the increased life expectancy guaranteed by early-stage detection of diseases such as cancer.
With LANTERNS (Lanthanide Ion Doping of Ternary Quantum Dots) I will tackle the major bottleneck of FI: the lack of luminescent contrast agents with bright NIR emission.
This project aims to combine the advantageous optical properties of semiconductor nanocrystals (aka, quantum dots) and those of NIR-emitting lanthanide ions, which are respectively strong light absorption and emission of photons in a narrow, biologically convenient spectral range. Quantum dots of copper indium sulfide (CuInS2) will be doped with ions of neodymium, erbium, ytterbium and holmium, all displaying NIR emission. CuInS2 is the chosen semiconductor material since it absorbs photons up to 830 nm (well into the NIR). After absorbing this optical energy, CuInS2 is expected to transfer it to the doped lanthanide, ultimately leading to emission of photons of longer wavelength (sensitized emission; Figure 2). Modification of the surface chemistry of the lanthanide-doped quantum dots will ensure water dispersibility, lack of cytotoxicity, and the capability to target tissues (e.g. solid tumors), overall guaranteeing their applicability as FI contrast agents.
FINAL CONCLUSIONS:
1. Semiconductor-based nanocrystals were identified as the most promising contrast agents for FI and other optical diagnostic approaches (e.g. optical coherence tomography).
2. Methods to increase the brightness (the product of absorption and emission efficiencies) of available luminescent semiconductor nanocrystals were identified. Novel, efficient semiconductor nanocrystals were designed.
3. Although during the action a paradigm shift occurred - redirecting the effort towards undoped semiconductor nanocrystals - an in-depth literature survey allowed defining the guidelines to prepare the initially targeted class of materials: lanthanide-doped semiconductor nanocrystals.
