Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity

Dalton Trans. 2015 Mar 7;44(9):4016-31. doi: 10.1039/c4dt03210a.

Abstract

The relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles is the result of the complex interplay between the nanoparticle size, the water exchange rate and the chelate structure. In this work we study the effect of the length of ω-thioalkyl linkers, anchoring fast water exchanging Gd(3+) chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(α-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25 °C), were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggest that functionalized gold nanoparticles hold great potential for further investigation as MRI contrast agents. This study contributes to a better understanding of the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a relevant contribution towards "design rules" for nanostructures functionalized with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacokinetics
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacokinetics
  • Gadolinium / chemistry*
  • Gadolinium / pharmacokinetics
  • Gold / chemistry*
  • Gold / pharmacokinetics
  • Male
  • Metal Nanoparticles / chemistry*
  • Mice
  • Rats, Wistar
  • Tissue Distribution
  • Water / chemistry

Substances

  • Chelating Agents
  • Contrast Media
  • Coordination Complexes
  • Gd(DO3A-N-alpha-aminopropionate)
  • Water
  • Gold
  • Gadolinium