The biobehavior, biocompatibility and theranostic application of SPNS and Pd@Au nanoplates in rats and rabbits

On account of the fascinating surface plasmon resonance (SPR) properties, the ability of passively targeting tumors and remarkable biocompatibility, two-dimensional (2D) Pd-based nanomaterials have demonstrated wide application prospects in cancer theranostics. However, the used animal models for exploring the bioapplications and biosafety of 2D Pd-based nanomaterials were usually limited to mice. To further widen their biomedical applications and promote future clinical transformation, it is necessary to make a breakthrough in animal models. In this work, Sprague Dawley (SD) rats and New Zealand rabbits were used as the experimental animals and orthotopic liver tumors or subcutaneous tumors were induced in these animals. Taking ≈5 nm small Pd nanosheets (SPNS) and 30 nm Pd@Au nanoplates (Pd@Au) as the representative 2D Pd-based nanomaterials, we investigated their biobehaviors and biosafety in rat liver & subcutaneous tumor models and rabbit liver tumors. The results indicated that SPNS and Pd@Au could still effectively accumulate on the tumor sites of these bigger animal models by the enhanced permeability and retention (EPR) effect, and the accumulation effects were closely related to their sizes. Metabolism studies confirmed that SPNS could be excreted out of rats through urine. Moreover, based on the sufficient uptake by cancer cells and passive accumulation of SPNS and Pd@Au in subcutaneous tumors in rats, we performed photothermal therapy (PTT) in vitro and in vivo. Significant tumor growth inhibition illustrated that even though the animal model was dozens of times bigger than the mouse model, the 2D Pd-based nanomaterials satisfied the requirements of being an outstanding photothermal reagent. Finally, the hematological and histological examination results suggested that SPNS and Pd@Au had favorable biocompatibility in rats and rabbits at a given dose. We hope this work will drive the development of 2D Pd-based nanomaterials towards practical clinical applications and provide a guide for other theranostic nanoplatforms that will be applied in bigger animal tumor models in the future.