Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive
microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein,
we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the
tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1
phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability,
while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo.
Combined with antigenic peptides, this nanovaccine could signi... More
Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive
microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein,
we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the
tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1
phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability,
while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo.
Combined with antigenic peptides, this nanovaccine could significantly increase the infiltration of
CD8+ T cells into tumor tissue and strongly activate dendritic cells in sentinel lymph nodes. Finally,
we used the dual-modified nanoparticles to first convert the tumor microenvironment and then the
nanovaccine administration in a TC1 tumor model to further enhance efficacy. This strategy inhibited
tumor growth and achieved a 40% cure rate in mice (two of five). In summary, this study provides a
potent and rationally designed nanoadjuvant to enhance antitumor efficiency and facilitate delivery
of neoantigen vaccines by repolarizing TAMs and harmonizing immune cells.
