Desarrollo de nanosistemas con múltiple diana para vectorización y potenciación de la actividad antitumoral de CAR-T (Chimeric Antigen Receptor T-Cell) en inmunoterapia contra neuroblastoma

Neuroblastoma is a type of cancer that forms in immature nerve tissue, appearing mainly in the adrenal glands, and is present almost exclusively in early childhood. It is the most common extracranial solid tumor in children, and accounts for 15% of childhood cancer deaths. The treatments used today to combat the disease are based on a combination of different techniques, such as surgery, chemotherapy, radiotherapy or immunotherapy, treatments that can be too harmful in childhood. Even so, high-risk cases of neuroblastoma continue to have a mortality rate of 50%, which makes it necessary to search for new alternatives capable of improving the treatment of the disease and reducing its side effects. In recent years, the development of immunotherapy based on CAR-T cells (Chimeric Antigenic Receptor T-Cell) has revolutionized the treatment of liquid tumors. However, the existence of an immunosuppressive microenvironment and the lack of tumor-specific surface antigens have made the results in solid tumors such as neuroblastoma less successful. In this work, we have studied the ability of nanocarriers based on protocell systems to produce signaling in the membrane of neuroblastoma cells allowing the vectorization of CAR-T cells while introducing their contents into the cell cytoplasm.In addition, the cytotoxic activity of two protocell-based nanocarrier systems capable of transporting horseradish peroxidase enzyme to neuroblastoma tumor cells in two different ways have been developed and compared: wrapped in nanocapsules anchored to the outside of the protocell, or loaded inside the silica pores. This enzyme would be able to oxidize indole-3-acetic acid to different free radical compounds that would cause apoptosis and cell death. The protocell system with peroxidase nanocapsules anchored to its exterior has been found to be much more effective in decreasing cell viability when combined with indole-3-acetic acid.