Multifunctional mesoporous nanoparticles as pH-responsive Fe2+ reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth

Artemisinin (ART) is an iron-dependent anti-cancer drug. However, simultaneous delivery of hydrophobic ART and Fe2+ ions into cancer cells remains a major challenge. Herein, we reported Fe3O4@C/Ag@mSiO(2) (FCA@mSiO(2)) multifunctional nanocarriers which can load ART as high as 484 mg/g. Moreover, FCA@InSiO2 nanoparticles demonstrated pH-responsive Fe2+ release, the concentration of Fe2+ ions can reach 2.765 nmol/L in HeLa cells cultured with FCA@mSiO(2) nanoparticles. The antitumor efficacy of ART-loaded FCA@mSiO(2) nanoparticles measured by MU assay was significantly enhanced compared with free ART. It was suggested that the ART-loaded FCA@InSiO2 nanoparticles are internalized by HeLa cells and located at the acidic compartments of endosomes and lysosomes, releasing Fe2+ ions to non-enzymatically convert ART to toxic products for killing cancer cells. This result provides a way for using promising natural drugs in anti-cancer therapeutics. (C) 2014 Elsevier Ltd. All rights reserved.