Multifunctional mesoporous nanoparticles as pH-responsive Fe(2+) reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth

Jian Chen; Zhen Guo; Hai-Bao Wang; Jia-Jia Zhou; Wei-Jie Zhang; Qian-Wang Chen

doi:10.1016/j.biomaterials.2014.04.028

Multifunctional mesoporous nanoparticles as pH-responsive Fe(2+) reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth

Biomaterials. 2014 Aug;35(24):6498-507. doi: 10.1016/j.biomaterials.2014.04.028. Epub 2014 May 5.

Authors

Jian Chen¹, Zhen Guo², Hai-Bao Wang³, Jia-Jia Zhou⁴, Wei-Jie Zhang⁵, Qian-Wang Chen⁶

Affiliations

¹ Hefei National Laboratory for Physical Sciences at Microscale, China & Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Materials Science & Engineering, CAS High Magnetic Field Laboratory, University of Science and Technology of China, Hefei 230026, China.
² Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China. Electronic address: [email protected].
³ Radiology Department of the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address: [email protected].
⁴ Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
⁵ Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
⁶ Hefei National Laboratory for Physical Sciences at Microscale, China & Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Materials Science & Engineering, CAS High Magnetic Field Laboratory, University of Science and Technology of China, Hefei 230026, China. Electronic address: [email protected].

PMID: 24797880
DOI: 10.1016/j.biomaterials.2014.04.028

Abstract

Artemisinin (ART) is an iron-dependent anti-cancer drug. However, simultaneous delivery of hydrophobic ART and Fe(2+) ions into cancer cells remains a major challenge. Herein, we reported Fe3O4@C/Ag@mSiO2 (FCA@mSiO2) multifunctional nanocarriers which can load ART as high as 484 mg/g. Moreover, FCA@mSiO2 nanoparticles demonstrated pH-responsive Fe(2+) release, the concentration of Fe(2+) ions can reach 2.765 nmol/L in HeLa cells cultured with FCA@mSiO2 nanoparticles. The antitumor efficacy of ART-loaded FCA@mSiO2 nanoparticles measured by MTT assay was significantly enhanced compared with free ART. It was suggested that the ART-loaded FCA@mSiO2 nanoparticles are internalized by HeLa cells and located at the acidic compartments of endosomes and lysosomes, releasing Fe(2+) 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.

Keywords: Fe(2+) ions reservoirs; Free radicals; Hydropobic artemisinin vehicles; Mesoporous magnetic nanocarriers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Artemisinins / pharmacology*
Cell Death / drug effects
Cell Proliferation / drug effects
Drug Carriers / chemistry*
Endocytosis / drug effects
Ferric Compounds / chemistry
HeLa Cells
Humans
Hydrogen-Ion Concentration
Iron / pharmacology*
MCF-7 Cells
Nanoparticles / chemistry*
Nanoparticles / toxicity
Nanoparticles / ultrastructure
Neoplasms / pathology*
Porosity
Silicon Dioxide / chemistry
Silver / chemistry
Spectrophotometry, Ultraviolet
Spectroscopy, Fourier Transform Infrared
X-Ray Diffraction

Substances

Artemisinins
Drug Carriers
Ferric Compounds
ferric oxide
Silver
Silicon Dioxide
artemisinin
Iron