DTPAA-Gd Functionalized Ultrasmall Au15NCs Nanohybrids for Multimodal Imaging

Int J Nanomedicine. 2020 Jan 14:15:227-238. doi: 10.2147/IJN.S227169. eCollection 2020.

Abstract

Introduction: Multimodal imaging agent has the potential to overcome the shortage and incorporate the advantages of different imaging tools for extremely sensitive diagnosis. To achieve multimodal imaging, combining multiple contrast agents into a special nanostructure has become a main strategy; However, the combination of all of these functions into one nanoplatform usually requires a complicated synthetic procedure that results in heterogeneous nanostructure.

Methods: In this study, we develop ultrasmall gold nanoclusters with 15 gold atoms (Au15NCs) functionalized with diethylenetriamine-pentaacetic acid dianhydride (DTPAA-Gd) as an optimized multimodal imaging agent to enhance imaging ability.

Results: The Au15NCs-DTPAA-Gd nanohybrids possess the ultra-small size and are capable of enhancing the contrast in near-infrared fluorescence (NIRF), magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Meanwhile, the integrated DTPAA-Gd component not only endow the nanohybrids to produce higher T1 relaxivity (r1 = 21.4 mM-1 s-1) than Omnipaque (r1 = 3.973 mM-1s-1) but also further enhance X-ray attenuation property of Au15NCs. Importantly, the fluorescence intensity of Au15NCs-DTPAA-Gd did not decrease compared with Au15NCs. Ultimately, in vivo imaging experiments have demonstrated that Au15NCs-DTPAA-Gd nanohybrids can be quickly eliminated from the body through the urinary system and has great potential for anatomical imaging.

Conclusion: These data manifest Au15NCs-DTPAA-Gd present great potential as a multimodal contrast agent for disease diagnosis, especially for early accurate detection of tumors.

Keywords: X-ray computed tomography; magnetic resonance imaging; multimodal imaging; near-infrared fluorescence; ultrasmall gold nanoclusters.

MeSH terms

  • Anhydrides / chemistry*
  • Anhydrides / pharmacokinetics
  • Animals
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Fluorescence
  • Gadolinium / chemistry
  • Gold / chemistry*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Magnetic Resonance Imaging / methods
  • Mice, Inbred BALB C
  • Multimodal Imaging / methods*
  • Nanocomposites / chemistry*
  • Pentetic Acid / chemistry*
  • Pentetic Acid / pharmacokinetics
  • Polyamines / chemistry
  • Spectroscopy, Near-Infrared
  • Tissue Distribution
  • Tomography, X-Ray Computed / methods

Substances

  • Anhydrides
  • Contrast Media
  • Polyamines
  • diethylenetriamine pentaacetic acid dianhydride
  • Gold
  • Pentetic Acid
  • Gadolinium