Non-cytotoxic carbon nanotubes bioconjugated with fucosyltransferase 4-derived peptides modulate macrophage polarization in vitro

Abstract In recent years, nanotechnology has had an important development in nanoparticle-based therapies. Carbon nanotubes (CNTs) are among the most valuable nanoparticles, given their physicochemical properties and functionalization possibilities; therefore, they are proposed as peptide carriers in immunotherapies. Immunotherapy has been explored as a promising therapy in ovarian cancer (OvCa), and it has been reported that macrophage polarization into M1 and M2 phenotypes plays a pivotal role in OvCa initiation, progression, and metastasis, providing therapeutic targets for macrophage-targeted treatment. In this work, we explored the initial stages for the design of CNTs-based immunotherapy for ovarian cancer (OvCa) using fucosyltransferase-4-derived T cell epitopes conjugated with CNTs ( f -CNTs). Their cytotoxicity and biological interactions were analyzed in macrophages (J774A.1) and human ovarian cancer cells (SKOV-3). Here we showed that f -CNTs do not show cytotoxicity signs in concentrations < 6 µg/mL; additionally, they induced morphological changes and activation in macrophages, time-dependent uptake in lysosomes, production of M1-like cytokines, upregulation of CD80, CD86, and MHC II, and downregulation of ARG-1. In conclusion, f -CNTs exhibited biocompatibility in both cell lines and displayed M1-like polarization in macrophages, allowing us to propose them as a peptide carrier system for macrophage activation and polarization for being explored in ovarian cancer immunotherapies.