Synthesis and characterization of dual radiolabeled layered double hydroxide nanoparticles for use in in vitro and in vivo nanotoxicology studies

Layered double hydroxide (LDH) nanomaterials are currently the focus of intense scientific interest due to their potential application in drug and gene delivery research. However, the emerging field of nanotoxicology requires the development of new and more sensitive methodologies to follow the in vivo delivery kinetics as well as the persistence and bioaccumulation of the LDH carriers subsequent to delivery of the payload to the target area. Radioisotopic labeling offers very high detection sensitivity (<10-14 moles) and straightforward quantitation with respect to other labeling techniques. We have shown that incorporation of naturally occurring Co²⁺ and Ga ³⁺ cations into the LDH structure has a negligible effect on the physiochemical properties of the pristine nanoparticles. Radiolabeling through dual isomorphous substitution of 57Co²⁺ and 67Ga³⁺ into the LDH structure offers the utility to accurately track and also follow the structural dissolution of these nanomaterials over a range of biologically relevant pHs. Radiolabeled-LDH kinetic release profiles in conjunction with transmission electron microscopy and X-ray diffraction studies have revealed that the bulk dissolution of LDH occurs with no preferential leaching of the 57Co²⁺ or 67Ga³⁺ metal species from the crystal structure. Furthermore, the present study clearly demonstrates how radiolabeling methodologies described here may be adapted for use in other similar clay systems and allow for the first time noninvasive imaging and monitoring of the fate of nanoparticles.