Spontaneously formed porous structure and M1 polarization effect of Fe3O4 nanoparticles for enhanced antitumor therapy

Fe3O4-DOX+HA was prepared via pore adsorption and electrostatic interaction on the basis of “formed porous structure” of spontaneously assembled Fe3O4 nanoparticles; After intravenous injection, Fe3O4-DOX+HA could specifically accumulated in tumor cells and TAMs via CD44 specific targeting of HA; M1 polarization ability in tumor tissues of Fe3O4-DOX+HA was achieved by the assist of HA-based TAM targeting and macrophage recruitment of Fe3O4 nanoparticles; The combination treatment of DOX mediated tumor cell killing and Fe3O4 nanoparticles mediated M1 macrophages polarization dramatically enhanced antitumor efficacy. [Display omitted] In this study, we developed a novel Fe3O4 nanoparticles-doxorubicin (DOX)-Hyaluronic acid (HA) nanoparticles on the basis of firstly discovered “formed porous structure” in spontaneously assembled Fe3O4 nanoparticles. The Mechanism of Action (MOA) behind this porous DOX-loading cargo was tested and confirmed. A multi-functional Fe3O4-DOX+HA nanoparticle was further constructed by incorporating HA into our system. In vitro and in vivo studies exhibited that Fe3O4-DOX+HA owned enhanced antitumor efficacy with significantly prolonged survival time due to the combination of M1 polarization ability of Fe3O4 nanoparticles, tumor killing effect of DOX and tumor and TAM-targeting effect of HA. All in all, our studies offer a novel strategy to develop a multifunctional antitumor system with a simple preparation method and an enhanced therapeutic outcome.