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.