Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins

J Am Chem Soc. 2007 Jul 18;129(28):8845-9. doi: 10.1021/ja0719780. Epub 2007 Jun 23.


An MCM-41-type mesoporous silica nanoparticle (MSN) material with a large average pore diameter (5.4 nm) is synthesized and characterized. The in vitro uptake and release profiles of cytochrome c by the MSN were investigated. The enzymatic activity of the released protein was quantitatively analyzed and compared with that of the native cytochrome c in physiological buffer solutions. We found that the enzymes released from the MSNs are still functional and highly active in catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) by hydrogen peroxide. In contrast to the fact that cytochrome c is a cell-membrane-impermeable protein, we discovered that the cytochrome c-encapsulated MSNs could be internalized by live human cervical cancer cells (HeLa) and the protein could be released into the cytoplasm. We envision that these MSNs with large pores could serve as a transmembrane delivery vehicle for controlled release of membrane-impermeable proteins in live cells, which may lead to many important biotechnological applications including therapeutics and metabolic manipulation of cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Membrane Permeability / drug effects
  • Cytochromes c / administration & dosage
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Porosity
  • Silicon Dioxide / pharmacokinetics
  • Silicon Dioxide / therapeutic use*


  • Drug Carriers
  • Silicon Dioxide
  • Cytochromes c