Design and Synthesis of Gold-Gadolinium-Core-Shell Nanoparticles as Contrast Agent: a Smart Way to Future Nanomaterials for Nanomedicine Applications.
Introduction
The development of biopolymers for the synthesis of Gd(III) nanoparticles, as therapeutics, could play a key role in nanomedicine. Biocompatible polymers are not only used for complex monovalent biomolecules, but also for the realization of multivalent active targeting materials as diagnostic and/or therapeutic hybrid nanoparticles. In this article, it was reported for the first time, a novel synthesis of Gd(III)-biopolymer-Au(III) complex, acting as a key ingredient of core-shell gold nanoparticles (Gd(@AuNPs).


Material and methods
The physical and chemical evaluation was carried out by spectroscopic analytical techniques (Raman spectroscopy, UV-visible and TEM). The theoretical characterization by DFT (density functional theory) analysis was carried out under specific conditions to investigate the interaction between the Au and the Gd precursors, during the first nucleation step. Magnetic features with relaxivity measurements at 7T were also performed as well as cytotoxicity studies on hepatocyte cell lines for biocompatibility studies. The in vivo detailed dynamic biodistribution studies in mice to characterize the potential applications for biology as MRI contrast agents were then achieved.


Results
Physical-chemical evaluation confirms the successful design and reaction supposed. Viabilities of TIB-75 (hepatocytes) cells were evaluated using Alamar blue cytotoxic tests with increasing concentrations of nanoparticles. In vivo biodistribution studies were then accomplished to assess the kinetic behavior of the nanoparticles in mice and characterize their stealthiness property after intravenous injection.


Conclusion
We demonstrated that Gd@AuNPs have some advantages to display hepatocytes in the liver. Particularly, these nanoconjugates give a good cellular uptake of several quantities of Gd@NPs into cells, while preserving a T1 contrast inside cells that provide a robust in vivo detection using T1-weighted MR images. These results will strengthen the role of gadolinium as complex to gold in order to tune Gd(@AuNPs) as an innovative diagnostic agent in the field of nanomedicine.
['Aouidat|Fatima|F|', 'Boumati|Sarah|S|', 'Khan|Memona|M|', 'Tielens|Frederik|F|0000-0002-6760-6176', 'Doan|Bich-Thuy|BT|', 'Spadavecchia|Jolanda|J|']
D000818:Animals D016923:Cell Death D002470:Cell Survival D003287:Contrast Media D065546:Drug Liberation D005682:Gadolinium D006046:Gold D007700:Kinetics D008279:Magnetic Resonance Imaging D053768:Metal Nanoparticles D008807:Mice, Inbred BALB C D050997:Nanomedicine D011108:Polymers D014018:Tissue Distribution
relaxivity biodistribution MRI Gd-gold complex theoretical study