Noncytotoxic Carbon Nanotubes Bioconjugated with Fucosyltransferase 4-Derived Peptides Modulate Macrophage Polarization In Vitro

Abstract

Important developments in nanoparticle-based therapies have occurred in recent years. Carbon nanotubes (CNTs) are among the most valuable nanoparticles because of their physicochemical properties and functionalization possibilities; therefore, they are proposed as peptide carriers for immunotherapy. Immunotherapy has been explored as a promising treatment for ovarian cancer (OvCa), and it has been reported that macrophage polarization to 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 of designing CNT-based immunotherapy for 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, f-CNTs did not show cytotoxicity at 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 major histocompatibility complex II (MHC II); and downregulation of arginase-1 (ARG-1). In conclusion, f-CNTs exhibited biocompatibility in both cell lines and displayed M1-like polarization in macrophages, and we propose their exploration as a peptide carrier system for macrophage activation and polarization in ovarian cancer immunotherapy.