Adoptive transfer of Fe3O4-SWCNT engineered M1-like macrophages for magnetic resonance imaging and enhanced cancer immunotherapy

Abstract

Macrophage-based tumor immunotherapy can effectively kill tumor cells in a direct manner when tumor specific antigens are idle or unknown. However, the presence of M2-like tumor associated macrophages (TAMs) would limit the treatment efficiency. Therefore, reversing the M2-like TAMs phenotype to regulate the immunosuppressive tumor microenvironment (TME) is crucial. Herein, we proposed nano-sized ferroferric oxide/single wall carbon nanotubes composites (Fe₃O₄-SWCNT) to engineer the macrophages species for powerful cancer therapy. The synthesized Fe₃O₄-SWCNT revealed good magnetic resonance imaging (MRI) performance, which enabled in vivo tracking of macrophage mediated immunotherapy. In addition, Fe₃O₄-SWCNT engineered M1-like macrophages (Fe₃O₄-SWCNT@M1) could maintain M1 phenotype, migrate to tumor cells and release nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α). A series of experimental results showed that Fe₃O₄-SWCNT@M1 could effectively promote the polarization of endogenous M2-like macrophages to M1-like macrophages, activate tumor immune response and inhibit tumor progression. This work is expected to provide a new vision for macrophage-based tumor immunotherapy.

Keywords: Engineered M1-like macrophages; Fe(3)O(4)-SWCNT; M2-like TAMs repolarization; Magnetic resonance imaging; Tumor immunotherapy.