Fabrication of deferasirox-decorated aptamer-targeted superparamagnetic iron oxide nanoparticles (SPION) as a therapeutic and magnetic resonance imaging agent in cancer therapy

J Biol Inorg Chem. 2021 Feb;26(1):29-41. doi: 10.1007/s00775-020-01834-8. Epub 2020 Nov 6.

Abstract

In the current study, the synthesis of a theranostic platform composed of superparamagnetic iron oxide nanoparticles (SPION)-deferasirox conjugates targeted with AS1411 DNA aptamer was reported. In this regard, SPION was amine-functionalized by (3-aminopropyl)trimethoxysilane (ATPMS), and then deferasirox was covalently conjugated onto its surface. Finally, to provide guided drug delivery to cancerous tissue, AS1411 aptamer was conjugated to the complex of SPION-deferasirox. The cellular toxicity assay on CHO, C-26 and AGS cell lines verified higher cellular toxicity of targeted complex in comparison with non-targeted one. The evaluation of in vivo tumor growth inhibitory effect in C26 tumor-bearing mice illustrated that the aptamer-targeted complex significantly enhanced the therapeutic outcome in comparison with both non-targeted complex and free drug. The diagnostic capability of the prepared platform was also evaluated implementing C26-tumor-bearing mice. Obtained data confirmed higher tumor accumulation and higher tumor residence time for targeted complex through MRI imaging due to the existence of SPION as a contrast agent in the core of the prepared complex. The prepared multimodal theranostic system provides a safe and effective platform for fighting against cancer.

Keywords: Aptamer; Cytotoxicity; Deferasirox; Drug delivery; SPION.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / therapeutic use*
  • Aptamers, Nucleotide / chemistry
  • CHO Cells
  • Cell Line, Tumor
  • Contrast Media / chemical synthesis
  • Contrast Media / therapeutic use*
  • Cricetulus
  • Deferasirox / chemistry
  • Deferasirox / therapeutic use*
  • Female
  • Humans
  • Immobilized Nucleic Acids / chemistry
  • Immobilized Nucleic Acids / therapeutic use
  • Iron Chelating Agents / chemical synthesis
  • Iron Chelating Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry
  • Magnetite Nanoparticles / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / drug therapy*
  • Precision Medicine
  • Propylamines / chemistry
  • Silanes / chemistry

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Contrast Media
  • Immobilized Nucleic Acids
  • Iron Chelating Agents
  • Magnetite Nanoparticles
  • Propylamines
  • Silanes
  • 3-aminopropyltrimethoxysilane
  • Deferasirox