Stem cell-mediated delivery of nanogels loaded with ultrasmall iron oxide nanoparticles for enhanced tumor MR imaging

Nanoscale. 2019 Mar 14;11(11):4904-4910. doi: 10.1039/c8nr10490e.

Abstract

The development of new nanoplatforms with enhanced tumor accumulation for accurate diagnosis still remains a great challenge in current precision nanomedicine. Herein, we report the design of stem cell-mediated delivery of nanogels (NGs) loaded with ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) for enhanced magnetic resonance (MR) imaging of tumors. In this study, sodium citrate-stabilized ultrasmall Fe3O4 NPs with a size of 3.16 ± 1.30 nm were first synthesized using a solvothermal route, coated with polyethyleneimine (PEI), and used as crosslinkers to crosslink alginate (AG) NGs formed via a double emulsion approach, where the AG carboxyl groups were pre-activated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The thus prepared Fe3O4 NP-loaded NGs (AG/PEI-Fe3O4 NGs) with a size of 47.68 ± 3.41 nm are water-dispersible, colloidally stable, cytocompatible in a given concentration range, display a relatively high r1 relaxivity (r1 = 1.5 mM-1 s-1), and are able to be taken up by bone mesenchymal stem cells without compromising cell viability and stem cell characteristics. Due to the tumor-chemotaxis or tumor tropism, the BMSCs are able to mediate the enhanced delivery of AG/PEI-Fe3O4 NGs to the tumor site after intravenous injection, thus enabling significantly strengthened MR imaging of tumors when compared to free NGs. These findings suggest that the developed AG/PEI-Fe3O4NGs, once mediated by stem cells may serve as a novel, safe, effective and targeted platform for enhanced MR imaging of tumors.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Cells, Cultured
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / cytology*
  • Mice, Inbred ICR
  • Neoplasms / diagnostic imaging*
  • Particle Size
  • Polyethyleneimine / chemistry
  • Transplantation, Heterologous

Substances

  • Alginates
  • Contrast Media
  • Magnetite Nanoparticles
  • Polyethyleneimine