Compounds containing gadolinium, a metal with magnetic properties that help highlight tumors, blood vessels or damaged tissue, are commonly used as contrast agents in MRI. Although these compounds have been essential for medical diagnosis for almost four decades, their use may pose a health risk for patients with kidney failure.
They also contribute to the persistence of gadolinium in the environment, since they can enter wastewater and are difficult to eliminate during its treatment.
Therefore, safer and more sustainable alternatives are being sought. Currently under study is the use of metals considered safer and more abundant, such as manganese, which is also more cost effective than other heavy metals.
The aim of this study was to develop an initial manganese-doped carbon nanodot platform that would be stable, reproducible, well-tolerated and detectable using magnetic resonance imaging (MRI). "Despite the great potential of these materials and their numerous possible applications, achieving adequate stability and reproducibility remains one of the main challenges in translating them from research to real-world biomedical applications. Through our work, as well as optimizing synthesis, we have also (and importantly) established validation strategies that allow us to obtain a truly reliable and reproducible material", commented Cardo.
"An important contribution of this work was that the nanodots could be detected in their natural form using MRI", says CIC biomaGUNE researcher Michele Cesco, lead author of the paper, "without having to first add a molecule that targets them toward a specific organ or tissue, something that usually contributes to their accumulation and, hence, their detection."
Studies using animal models show that the nanoparticles are efficiently eliminated from the body and are highly biocompatible, even after long-term studies. Once good contrast-agent performance had been achieved; that is, a very high detectability using traditional MRI, comparable to that of commercial contrast agents, "we were able to study the behavior of the material itself. For example, we studied how the material behaved over the long term, in both cells and animals, and observed adequate biodistribution and rapid elimination from the body, without detecting any significant toxic effects on the main organs analyzed", added Cardo. The results support their potential as next-generation manganese-based contrast agents, since they offer efficacy, stability and safety.
There is a growing need in medicine for increasingly versatile contrast agents that can be used in different imaging techniques, such as magnetic resonance imaging and positron emission tomography (PET), and can also combine diagnosis and treatment. The nanoparticles designed at CIC biomaGUNE have fluorescent properties, opening up the possibility of also using them with other detection techniques and combining different imaging modalities in the one particle.
In general, carbon nanodots have great potential for theranostics (diagnosis and therapy combined) applications; that is, combining in the same platform the ability to detect and to treat a disease. The next step is to move forward in this direction: "We are working to retain the high MRI detection capabilities and to add new functions that allow the nanoparticles to be targeted to certain diseases, such as cancer (and detect it using MRI), and the incorporation of a therapeutic action. In particular, we are working on light-activated therapeutic functions, and the results are looking very promising", concluded the researchers.