Nitroxide-radicals-modified gold nanorods for in vivo CT/MRI-guided photothermal cancer therapy

Int J Nanomedicine. 2018 Nov 6:13:7123-7134. doi: 10.2147/IJN.S171804. eCollection 2018.

Abstract

Purpose: This article presents a report of the synthesis, characterization, and biomedical application of nitroxide-radicals-modified gold nanorods (Au-TEMPO NRs) for imaging-guided photothermal cancer therapy.

Patients and methods: Au nanorods were synthesized through seed-mediated growth method, 4-Amino-TEMPO was added and the reaction proceeded under magnetic stirring.

Results: With a mean length of 39.2 nm and an average aspect ratio of approximately 3.85, Au-TEMPO NRs showed good photothermal ability when they were irradiated by 808-nm laser. Au-TEMPO NRs could be stored in PBS for more than 1 month, showed no cytotoxicity against both tumor and normal cells at a concentration of up to 3 mg/mL, and functioned as a dual-mode contrast agent for CT/magnetic resonance (MR) imaging in vitro and in vivo, due to their high X-ray attenuation of Au and good r1 relaxivity of nitroxide radicals. Further, they had a long retention time (~4 hours) in the main organs, which enabled a long CT/MR imaging time window for diagnosis. Bio-distribution results revealed that these Au-TEMPO NRs passively aggregated in the liver and spleen. After irradiation by 808-nm laser, Au-TEMPO NRs could ablate the solid tumor in 4T1 tumor-bearing mice, which implied they were a potential theranostic agent for dual-mode imaging and photothermal cancer therapy.

Conclusion: This type of Au-TEMPO NRs with the abilities of CT/MR imaging and photothermal therapy, can play an active role in imaging-guided photothermal cancer therapy.

Keywords: Au NRs; PTT; TEMPO; computed tomography; magnetic resonance imaging.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cyclic N-Oxides / chemistry
  • Female
  • Gold / chemistry*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hyperthermia, Induced*
  • Liver
  • Magnetic Resonance Imaging*
  • Mice, Inbred BALB C
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Neoplasms / diagnostic imaging
  • Neoplasms / therapy*
  • Nitrogen Oxides / chemistry*
  • Phototherapy*
  • Static Electricity
  • Temperature
  • Tissue Distribution / drug effects
  • Tomography, X-Ray Computed*
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Cyclic N-Oxides
  • Nitrogen Oxides
  • 4-amino-TEMPO
  • Gold
  • nitroxyl