Fluorescent Magneto-Plasmonic Cyclodextrin Nanohybrids for Liquid Biopsy-Based Early Detection of Melanoma

Melanoma is one of the most aggressive cancers and the deadliest form of skin cancer with a rapidly increasing incidence in western populations. Its high metastatic potential is linked to increased cellular dissemination through a multistep process involving tumour growth and detachment from primary site. Therefore, early detection of melanoma cells and circulating tumour cells (CTCs) before the establishment of metastasis, is a key goal in melanoma research. Liquid biopsy is a non-invasive alternative for the diagnosis and monitoring of tumour evolution that involves the isolation of tumour-derived components, such as CTCs and extracellular vesicles (EVs), from body fluids like blood and urine. Therefore, to improve the detection of melanoma cells, we evaluated the ability of magnetic nanostructures to identify melanoma cells. Fluorescent magneto-plasmonic cationic amphiphilic cyclodextrin based nanoassemblies (SC16NH3+/MHS-26/Ada-Rhod/HA, SC16NH3+/MHS-26/Ada-Rhod), with and without hyaluronic acid decoration, were synthetized and characterized. Their biocompatibility was demonstrated using THP-1-derived human macrophages. Red fluorescence emission revealed efficient uptake and cytoplasmic localization of nanoassemblies in melanoma cells compared to fibroblasts. Furthermore, to assess their ability to recognize CTCs, we analysed the uptake of nanoassemblies by suspension cultures of melanoma cells versus monocytes, simulating blood or lymph flow conditions. The fluorescence and magnetic properties of nanoassemblies, enabling magnetic separation of nanostructures-positive cells, showed higher internalization in melanoma cells than in monocytes. Finally, preliminary data showed uptake of nanoassemblies in EVs derived from microalgae (nanoalgosomes) and melanoma cells. These findings support the use of these magnetic nanostructures for selective targeting of tumour-derived components in liquid biopsies. Conclusion: The nanoassemblies studied could provide a non-invasive method to detect and label melanoma cells in vitro, circulating melanoma cells as well as tumour-secreted extracellular vesicles thus contributing to the emerging field of precision medicine. Acknowledgement: This work is supported by the MUR-PNRR through the NextGenerationEU program with the project SAMOTHRACE “SiciliAn MicrOnanoTecH Research And innovation CEnter”.