Thermodynamic stability and kinetic inertness of a Gd–DTPA bisamide complex grafted onto gold nanoparticles

Abstract

Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd(3+) complexes and greatly enhanced their kinetic inertness.

Combined Magnetic Resonance Imaging and Photodynamic Therapy Using Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units

“…Most clinically used contrast agents are based on paramagnetic (4f 7 ) gadolinium(III) ions, which interact with water molecules to improve the relaxation rates of the protons, enhancing the image contrast . The immobilisation of trivalent gadolinium units on the surface of gold nanoparticles dramatically increases the relaxation rate experienced by the protons of the water molecules in their vicinity . This can be partly traced to the effect on the rotational correlation time, which increases when the assembly rotates slowly, leading to greatly increased relaxivity per Gd 3+ ion.…”

“…This can be partly traced to the effect on the rotational correlation time, which increases when the assembly rotates slowly, leading to greatly increased relaxivity per Gd 3+ ion. In addition to this intrinsic enhancement, the presence of many gadolinium ions creates a multimeric effect on the relaxation of water protons due to the increased localised contrast agent concentration …”

“…[15] The immobilisation of trivalent gadolinium units on the surfaceo fg old nanoparticles dramatically increases the relaxation rate experienced by the protons of the water molecules in their vicinity. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] This can be partlyt raced to the effect on the rotational correlation time, which increases when the assembly rotatess lowly,l eading to greatly increased relaxivity per Gd 3 + ion. In addition to this intrinsic enhancement, the presence of many gadolinium ions createsamultimeric effect on the relaxation of water protons due to the increased localised contrasta gent concentration.…”

“…In addition to this intrinsic enhancement, the presence of many gadolinium ions createsamultimeric effect on the relaxation of water protons due to the increased localised contrasta gent concentration. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] All current clinicallya pproved gadolinium magnetic resonance contrast agents (such as Dotarem, showni nF igure 1a) are extracellularp robesw ith an on-specific biodistribution. One of the aims of the research described here is to add to the development of an ew generation of contrasta gents, which are able to recognise early reporterso fagiven pathology on the cellular surface.T he targetingo fo verexpressed membrane receptors using MRI is hampered by the very low concentration of such receptors and by the relatively low sensitivity of Gd 3 + contrast agents.…”

DNA–gadolinium–gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells

“…It is of note that shape of particles is increasingly emerging as an important design consideration in providing improvements in contrast [34] that potentially will further improve relaxivity yield of each Gd(III)-chelate, but might eventually also allow tuning to multiple independent constructs being visualized using the same contrast mechanism [43]. Conjugation of gadolinium chelates onto the gold nanoparticles further affords an additional capping preventing Gd(III) leaching, hence increasing their stability [44]. High thermostability is essential to avoid ill-effects of Gd(III) ions on cellular health that could compromise long-term detection of transplanted cells [45].…”