Pegylated magnetic mesoporous silica nanoparticles decorated with AS1411 Aptamer as a targeting delivery system for cytotoxic agents

Pharm Dev Technol. 2019 Nov;24(9):1063-1075. doi: 10.1080/10837450.2019.1569678. Epub 2019 Aug 8.

Abstract

Fulfilling the purpose of developing a NP with theragnostic capabilities, the current study describes the synthesis of an aptamer-functionalized PEG-coated SPION/mesoporous silica core-shell nanoparticle for concurrent cancer targeted therapy and magnetic resonance imaging. SPIONs were synthesized according to a thermal decomposition method and served as cores for SPION/mesoporous silica core/shell nanoparticles (MMSNs). Doxorubicin was then successfully loaded in MMSNs which were then coated with di-carboxylic acid functionalized polyethylene glycol (PEG-MMSNs). AS1411 aptamers were at the end covalently attached to NPs (APT-PEG-MMSNs). The mean diameter of synthesized NPs was about 89 nm and doxorubicin encapsulation efficacy was ≈67.47%. Results of MTT based cell cytotoxicity assay demonstrated a significantly higher toxicity profile for APT-PEG-MMSNs against MCF7 cells compared to non-decorated MMSNs, while no significant differences were spotted against NIH-3T3 cells. Meanwhile, formation of protein corona around APT-PEG-MMSNs in biological medium significantly attenuated observed cytotoxicity against MCF7 cell line. Examining NPs uptake by MCF7 cells using confocal laser scanning microscopy also confirmed superiority of APT-PEG-MMSNs over PEG-MMSNs. Finally, APT decorated NPs induced highest signal intensity reduction in T2-weighted images during in vitro MRI assay. In conclusion, developed NPs may serve as promising multifunctional vehicles for simultaneous cancer targeted therapy and MRI imaging.

Keywords: SPION; Silica nanoparticles; aptamer; protein corona; targeted nanoparticle.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology
  • Aptamers, Nucleotide / chemistry*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Delivery Systems
  • Humans
  • MCF-7 Cells
  • Magnets / chemistry
  • Mice
  • NIH 3T3 Cells
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy
  • Oligodeoxyribonucleotides / chemistry*
  • Polyethylene Glycols / chemistry
  • Porosity
  • Silicon Dioxide / chemistry*

Substances

  • AGRO 100
  • Antibiotics, Antineoplastic
  • Aptamers, Nucleotide
  • Oligodeoxyribonucleotides
  • Polyethylene Glycols
  • Silicon Dioxide
  • Doxorubicin