Hyaluronic acid modified doxorubicin loaded Fe3O4 nanoparticles effectively inhibit breast cancer metastasis

Abstract

Tumor-associated macrophages (TAMs) play a critical role in tumor survival and metastasis. Iron(II,III) oxide (Fe₃O₄) nanoparticles have been shown to induce M₁ macrophage polarization to initiate antitumor immunity and inhibit tumor metastasis. Hyaluronic acid (HA) modified doxorubicin (DOX) loaded Fe₃O₄ nanoparticles (Fe₃O₄–DOX–HA) have been constructed to mediate specific delivery of Fe₃O₄ nanoparticles to CD44-positive 4T1 tumor cells and tumor associated macrophages. Covalent conjugation of HA with DOX rendered nanoparticles with pH sensitivity, and further contributed to the prolonged circulation and enhanced tumor-specific accumulation in vivo. Furthermore, combining the M₁ polarization effect of the Fe₃O₄ nanoparticles and enhanced cytotoxicity, Fe₃O₄–DOX–HA demonstrated enhanced antitumor and anti-metastasis effects both in vitro and in vivo.