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

Int J Pharm. 2019 Mar 25:559:329-340. doi: 10.1016/j.ijpharm.2019.01.048. Epub 2019 Jan 31.

Abstract

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.

Keywords: M(1) polarization; Porous structure; Spontaneous assembled Fe(3)O(4) nanoparticles; Tumor and TAM targeting.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Cell Line
  • Cell Line, Tumor
  • Doxorubicin / chemistry
  • Female
  • Ferric Compounds / chemistry*
  • Hyaluronic Acid / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Porosity
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Ferric Compounds
  • ferric oxide
  • Doxorubicin
  • Hyaluronic Acid