Dysprosium-doped carbon dots for magnetic resonance imaging and theragnostic applications

Magnetic resonance imaging (MRI) is a powerful diagnostic tool that allows a precise investigation of the human body, anatomic structures, physiological functions, molecular composition of tissues, providing clear and three-dimensional images. The addition of a contrast agent (CA) has become a crucial step for enhancing image contrast. CAs have received a lot of attention in terms of research and development pursuing the preparation of an imaging probe with adequate biocompatibility, good colloidal stability, and improved relaxometric properties. After the advent of nanotechnologies, the use of magnetic nanostructured agents has been the main focus of MRI CAs development up to this point. Nanoscale materials have shown outstanding physical and chemical properties due to the improvement of surface-to-volume ratio and to the abundance of functionalization sites. Carbon quantum dots, also known as C-dots, are a novel type of nanomaterial that has been widely studied during the last few years. Due to their high fluorescence characteristics, biocompatibility, dimension, and low toxicity, carbon dots have been investigated as biosensors, gene transmitters, drug carriers, and bioimaging probes. The purpose of this work is the synthesis and characterization of dysprosium-doped carbon dots that could be suitable as MRI-negative CA application. The evolution and recent development of imaging techniques have brought MRI procedures to a higher level to adapt to the necessities of doing imaging exams in shorter times and with higher resolution. The dysprosium cation (Dy3+), having a high magnetic moment and short relaxation time, has been considered the best choice for contrast agents in high magnetic field MR imaging. A bottom-up approach was adopted, and every set of carbon dots was produced using a one-step microwave-mediated synthesis method. Two main classes of carbon dots were synthesized: carbon dots from citric acid and dysprosium chloride hexahydrate and carbon nitride dots, in which urea was added as a nitrogen source. Then, it was applied a step of purification that included centrifugation, filtration, and dialysis. Characterization techniques such as UV–Vis and Fluorescence spectroscopy, Fourier-transform Infrared spectroscopy, Atomic Force Microscopy, Transmission Electron Microscopy, Zeta Potential analysis, Mass spectrometry, Thermogravimetric analysis, and Electron Paramagnetic Resonance spectroscopy were used. Carbon quantum dots have shown a passive uptake in tumours and retention effect too and their dysprosium conjugated derivatives could be used as theragnostic tools. This new approach opens the way to both personalized medicine and imaging-guided therapy. In this context, the previously prepared carbon nitride dots were conjugated to Doxorubicin, a chemotherapeutic drug largely used for treating, among others, blood, bladder, breast, lungs and nerves cancers. For the conjugation process, EDC/NHS coupling was employed. The last step of the work included the analysis of the relaxometric properties and cellular imaging. Dysprosium is known to be potentially irritating, but the viability tests showed low toxicity levels. Additional cellular tests were conducted on cancer cells to evaluate the efficacy of the Doxorubicin-conjugated carbon nitride dots. These results were further discussed to evaluate the next challenges and future perspectives of both selective bioimaging and theragnostic applications.