Post-administration labeling with Palladium(II) ions enables ICP-MS-based determination of the biodistribution of...

Carbonized nanogels (CNGs) are carbon-based nanomaterials possessing excellent antibacterial and antiviral activities for treating infectious diseases. Thus, investigations of the biodistribution of CNGs are crucial in ensuring their biosafety for in vivo applications. In this study, we combined a labeling scheme, employing tetrachloropalladate (PdCl₄^2-) ions to selectively label the administered CNGs in solubilized tissue samples, and an automatic sample pretreatment scheme, using a knotted reactor to effectively separate the PdCl₄^2--labeled CNGs from the free PdCl₄^2- ions and the tissue matrices, to enable reliable and interference-free quantification of CNGs through measuring the signal intensities of Pd using inductively coupled plasma mass spectrometry (ICP-MS). After optimizing the labeling conditions and the separation scheme, we observed that the PdCl₄^2- ions bound strongly to the CNGs (dissociation constant: 23.0 nM), with the method's detection limits reaching 1.6 fg L^-1 and 0.9 μg L^-1 within working ranges from 10^-4 to 1 μg L^-1 and from 1 to 1000 μg L^-1, respectively. We verified the reliability and applicability of this analytical method through spike analyses of solubilized rat liver, spleen, kidney, lung, brain, and blood samples (recoveries ranging from 96 to 102%) and through analyses of these rat organ and tissue samples after giving rats an intravenous dose of CNGs (2.5 mg kg^-1 body weight). The biodistribution data indicated that these administered CNGs deposited mainly in the liver, lung, and spleen at 10 min and 1 h post-administration. Our study revealed that this post-administration labeling scheme coupled with ICP-MS allows accurate determination of the biodistribution of carbonized nanomaterials.