BiOmimetic fluorinated nanoProbes for multIscale Tumor detection by MRI and Advanced Raman techniques (OPTIMA)

The OPTIMA project aims at developing biomimetic Fluorinated NanoParticles (FNP) as bimodal imaging probes for multiscale detection of solid tumors. Such FNP are based on a fluorine-dense core that can be detected by 19F-Magnetic Resonance Imaging (19F-MRI) and Raman spectroscopy. With this approach the very same FNP can be seen by both in vivo whole body 19F-MRI on the (sub)millimeter scale, and Raman imaging (ex vivo) and in situ Raman spectroscopy (in vivo), up to the micrometer scale. Main objectives of the project will be: On one side, the production of bimodal FNP with enhanced sensitivity for tumor detection by:(1) Synthesizing novel branched fluorinated molecules with a higher number of 19F atoms, increasing both MRI and Raman signal intensity,(2)applying biomimetic strategies to obtain cell membrane coated FNP with prolonged in vivo circulation lifetime and enhanced tumor homing capability. On the other side, (3) optimization of deep Raman technologies enabling the detection of FNP in tissue will be pursued. In fact, novel deep Raman-based techniques such as micro-Spatially Offset Raman Spectroscopy (micro-SORS) and Time- Domain Diffuse Raman Spectroscopy (TD-DRS) will be optimized to detect FNP under increasingly demanding settings (i.e. excised whole organ and tumor, in situ exposed tumor, and in vivo trans-cutaneous detection). The final proof-of-concept study will be performed on a subcutaneous murine model of breast cancer. The purpose is demonstrating that biomimetic FNP can accumulate and label the tumor by sequential noninvasive tumor visualization by 19F-MRI and accurate identification of tumor margins on a smaller scale by Raman techniques. With an eye to clinical translation, this would disclose the potential of deep Raman techniques as a compact tool for intraoperative detection to aid the surgical resection of tumors. Although our proof-of-concept in vivo study is focused on a tumor model, this approach is potentially suitable for other biomedical applications (e.g. monitoring of inflammation progression, cardiovascular disorders, therapeutic cell tracking). In fact, fluorinated materials are a unique target in terms of innovation and appeal, as they can be regarded as twofold bio-orthogonal due to their chemical and biological inertness and the total absence of endogenous organic fluorine. Thus, in parallel to potential clinical applications, OPTIMA can pave the way to develop new fluorine-based Raman/MRI tags for multimodal labelling purposes, enabling the study of the distribution and dynamics of biomolecules in cells and tissues. Overall, OPTIMA holds promise for translation of scientific outcomes into a biomedical multiscale approach and for new biotechnological products that can have a great impact on life sciences and on global public health.