Smart multifunctional nanostructure for targeted cancer chemotherapy and magnetic resonance imaging

ACS Nano. 2011 Oct 25;5(10):7866-73. doi: 10.1021/nn202073m. Epub 2011 Sep 21.

Abstract

Targeted chemotherapy and magnetic resonance imaging of cancer cells in vitro has been achieved using a smart multifunctional nanostructure (SMN) constructed from a porous hollow magnetite nanoparticle (PHMNP), a heterobifunctional PEG ligand, and an aptamer. The PHMNPs were prepared through a three-step reaction and loaded with the anticancer drug doxorubicin while being functionalized with PEG ligands. Targeting aptamers were then introduced by reaction with the PEG ligands. The pores of the PHMNPs are stable at physiological pH, but they are subject to acid etching. Specific binding and uptake of the SMN to the target cancer cells induced by aptamers was observed. In addition, multiple aptamers on the surface of one single SMN led to enhanced binding and uptake to target cancer cells due to the multivalent effect. Upon reaching the lysosomes of target cancer cells through receptor-mediated endocytosis, the relatively low lysosomal pH level resulted in corrosion of the PHMNP pores, facilitating the release of doxorubicin to kill the target cancer cells. In addition, the potential of using SMN for magnetic resonance imaging was also investigated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / metabolism
  • Biological Transport
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / toxicity
  • Humans
  • Hydrogen-Ion Concentration
  • Ligands
  • Lysosomes / metabolism
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles / chemistry
  • Molecular Targeted Therapy / methods*
  • Nanostructures* / toxicity
  • Neoplasms / diagnosis*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Polyethylene Glycols / chemistry
  • Porosity

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Drug Carriers
  • Ligands
  • Magnetite Nanoparticles
  • Polyethylene Glycols
  • Doxorubicin