Epirubicin loaded super paramagnetic iron oxide nanoparticle-aptamer bioconjugate for combined colon cancer therapy and imaging in vivo

Eur J Pharm Sci. 2013 Oct 9;50(2):191-7. doi: 10.1016/j.ejps.2013.06.015. Epub 2013 Jul 5.

Abstract

Every year a large number of new cases of colorectal cancer are diagnosed in the world. Application of Epirubicin (Epi) in treatment of cancer has been limited due to its cardiotoxicity. Specific delivery of chemotherapy drugs is an important factor in reducing the side effects of drugs used in chemotherapy. Enhanced permeability, retention effect and magnetic resonance (MR) traceability of super paramagnetic iron oxide nanoparticles (SPION) make them a great candidate in cancer therapy and imaging. In this study, Epirubicin-5TR1 aptamer-SPION tertiary complex was evaluated for the imaging and treatment of murine colon carcinoma cells (C26 cells, target). For cytotoxic studies (MTT assay), C26 and CHO-K1 (Chinese hamster ovary cells, nontarget) cells were treated with either Epi or Epi-Apt-SPION tertiary complex. Internalization was evaluated by flow cytometry. Finally, Apt-SPION bioconjugate was used for imaging of cancer in vivo. Flow cytometric analysis showed that the tertiary complex was internalized effectively to C26 cells, but not to CHO-K1 cells. Cytotoxicity of Epi-Apt-SPION tertiary complex also confirmed internalization data. The complex was less cytotoxic in CHO-K1 cells when compared to Epi alone. No significant change in viability between Epi- and complex-treated C26 cells was observed. Magnetic resonance imaging (MRI) indicated a high level of accumulation of the nano-magnets within the tumor site. In conclusion Epi-Apt-SPION tertiary complex is introduced as an effective system for targeted delivery of Epi to C26 cells. Moreover this complex could efficiently detect tumors when analyzed by MRI and inhibit tumor growth in vivo.

Keywords: Aptamer; Colon cancer; Epirubicin; MRI; SPION.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry*
  • Antibiotics, Antineoplastic / therapeutic use
  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / therapeutic use
  • CHO Cells
  • Cell Line, Tumor
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / drug therapy
  • Cricetinae
  • Cricetulus
  • Diagnostic Imaging
  • Epirubicin / chemistry*
  • Epirubicin / therapeutic use
  • Ferric Compounds / chemistry*
  • Humans
  • MCF-7 Cells
  • Magnetic Phenomena
  • Mice
  • Mice, Inbred BALB C
  • Mucin-1 / genetics
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use

Substances

  • Antibiotics, Antineoplastic
  • Aptamers, Nucleotide
  • Ferric Compounds
  • Mucin-1
  • ferric oxide
  • Epirubicin