The biodistribution of gold nanoparticles designed for renal clearance

Abstract

Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate) shell can be established by X-ray imaging (owing to the X-ray absorption of the gold core) and by magnetic resonance imaging (MRI) since the DTDTPA shell was designed for the immobilization of paramagnetic gadolinium ions. However scintigraphy appears better suited for a biodistribution study owing to a great sensitivity. The successful immobilization of radioelements ((99m)Tc, (111)In) in the DTDTPA shell, instead of gadolinium ions, renders possible the follow up of Au@DTDTPA by scintigraphy which showed that Au@DTDTPA nanoparticles exhibit a safe behaviour after intravenous injection to healthy rats.

Spatial light modulator based active wide-field illumination for ex vivo and in vivo quantitative NIR FRET imaging

“…Our biodistribution results of FRET NIR pair match previous results [13,[21][22][23][24] suggesting that upon injection of radioactively or fluorophore labeled Tfn into nude mice, and the labeled Tfn can pass freely through various tissues and reach epithelial-and phagocytic-rich organs, such as liver, and spleen and kidney, rapidly. During circulation, the Tfn is potentially taken up by phagocytic cell-rich organs, such as liver and spleen leading to their clearance after phagocytosis from the animal [13,[21][22][23][24]. Although FD% signal at 6hr-post injection is detected mainly in liver, spleen and brain tissues with high Tfn uptake, the FD % signal after 24hr-post injection remains predominantly in the liver indicating the importance of this organ in the metabolism and catabolism of Tfn.…”

“…TfnR is predominantly expressed in liver and it is also expressed in kidney, spleen, brain and very low expression in heart [13,[21][22][23][24]. Thus, the heart is expected to exhibit much less internalization of Tfn than the other four organs.…”

Gold nanoparticles enlighten the future of cancer theranostics

“…173 Recently, numerous studies have described AuNPs designed to investigate whether their in vivo behaviors such as accumulation in healthy tissues and renal clearance cause unwanted effects. [184][185][186][187] For example, the glomerular filtration, biodistribution, and toxicity of glutathione (GSH)-and bovine serum albumin …”

Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications

“…In another independent work, the renal clearance of dithiolated polyaminocarboxylate-coated gold nanoparticles was reported. 41 In this work, the hydrodynamic size was as large as 6.6 nm, higher than the proposed value of 5.5 nm for the renal clearance barrier, but the nanoparticles can still induce a highly efficient renal clearance. 41 Therefore, this illustrates that stable ligands are as important as the hydrodynamic size in renal clearance of nanoparticles.…”