PEG-templated mesoporous silica nanoparticles exclusively target cancer cells

Nanoscale. 2011 Aug;3(8):3198-207. doi: 10.1039/c1nr10253b. Epub 2011 Jul 4.

Abstract

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Caveolin 1 / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacokinetics
  • Clathrin / metabolism
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Drug Delivery Systems / methods
  • Fluorescein-5-isothiocyanate / chemistry
  • Folic Acid / chemistry
  • Folic Acid / pharmacokinetics
  • Folic Acid Transporters / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Electron, Transmission
  • Models, Biological
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Particle Size
  • Polyethylene Glycols / chemistry*
  • Silicon Dioxide / chemistry*
  • Surface-Active Agents / chemistry

Substances

  • Antineoplastic Agents
  • Caveolin 1
  • Clathrin
  • Drug Carriers
  • Folic Acid Transporters
  • Surface-Active Agents
  • Polyethylene Glycols
  • Silicon Dioxide
  • Folic Acid
  • Fluorescein-5-isothiocyanate
  • Cisplatin