Ultrasmall superparamagnetic nanoparticles targeting E-selectin: synthesis and effects in mice in vitro and in vivo

Int J Nanomedicine. 2019 Jun 19;14:4517-4528. doi: 10.2147/IJN.S199571. eCollection 2019.

Abstract

Purpose: We developed a contrast agent for targeting E-selectin expression. We detected the agent using magnetic resonance imaging (MRI) in vivo in nude mice that had undergone nasopharyngeal carcinoma (NPC) metastasis. Methods: Sialyl Lewis X (sLeX) was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Hydrodynamic size, polydispersity index, and ζ-potential of USPIO-polyethylene glycol (PEG) nanoparticles and USPIO-PEG-sLeX nanoparticles were measured. Component changes in nanoparticles of USPIO, USPIO-PEG, and USPIO-PEG-sLeX were analyzed by thermogravimetric analysis and Fourier-transform infrared spectroscopy. A model of NPC metastasis to inguinal lymph nodes in nude mice was used to investigate characteristics of the USPIO-PEG-sLeX nanoparticles in vivo. We investigated the ability of the T2* value, change in T2* value (ΔT2* value), and enhancement rate (ER) to assess accumulation of USPIO-PEG-sLeX nanoparticles quantitatively in mice of a metastasis group and control group. Four MRI scans were undertaken for each mouse. The first scan (t0) was done before administration of USPIO-PEG-sLeX nanoparticles (0.1 mL) via the tail vein. The other scans were carried out at 0 (t1), 1 (t2), and 2 hours (t3) postinjection. The mean optical density was used to reflect E-selectin expression. Results: sLeX was labeled onto USPIO successfully. In vivo, there were significant interactions between the groups and time for T2* values after administration of USPIO-PEG-sLeX nanoparticles. Six parameters (T2* at t2, ΔT2* at t1, ΔT2* at t2, ER at t1, ER at t2, and ER at t3) were correlated with the mean optical density. Conclusion: USPIO-PEG-sLeX nanoparticles can be used to assess E-selectin expression quantitatively. Use of such molecular probes could enable detection of early metastasis of NPC, more accurate staging, and treatment monitoring.

Keywords: E-selectin; Sialyl Lewis X; contrast agent; iron oxide; molecular MRI; nasopharyngeal carcinoma.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dextrans / chemistry*
  • Dextrans / ultrastructure
  • Dynamic Light Scattering
  • E-Selectin / metabolism*
  • Female
  • Lymphatic Metastasis
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Metastasis
  • Oligosaccharides / metabolism
  • Polyethylene Glycols / chemistry
  • Sialyl Lewis X Antigen
  • Static Electricity
  • Thermodynamics

Substances

  • Dextrans
  • E-Selectin
  • Magnetite Nanoparticles
  • Oligosaccharides
  • Sialyl Lewis X Antigen
  • ferumoxtran-10
  • Polyethylene Glycols