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.

中文翻译：

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SPNS 和 Pd@Au 纳米板在大鼠和兔子中的生物行为、生物相容性和治疗诊断应用†

由于令人着迷的表面等离子共振（SPR）特性、被动靶向肿瘤的能力和卓越的生物相容性，二维（2D）钯基纳米材料在癌症治疗诊断中展现出广泛的应用前景。然而，用于探索二维钯基纳米材料的生物应用和生物安全性的动物模型通常仅限于小鼠。为了进一步拓宽其生物医学应用，推动未来的临床转化，有必要在动物模型上取得突破。本研究以SD大鼠和新西兰兔为实验动物，在这些动物中诱导原位肝肿瘤或皮下肿瘤。以约5 nm小Pd纳米片（SPNS）和30 nm Pd@Au纳米片（Pd@Au）为代表的二维Pd基纳米材料，研究了它们在大鼠肝脏和皮下肿瘤模型以及兔肝脏肿瘤中的生物行为和生物安全性。结果表明，SPNS和Pd@Au仍然可以通过增强渗透性和保留（EPR）效应在这些较大动物模型的肿瘤部位有效积累，并且积累效应与其大小密切相关。代谢研究证实SPNS可以通过大鼠尿液排出体外。此外，基于癌细胞的充分摄取以及SPNS和Pd@Au在大鼠皮下肿瘤中的被动积累，我们在体外和体内进行了光热疗法（PTT） 。显着的肿瘤生长抑制表明，尽管动物模型比小鼠模型大几十倍，但二维钯基纳米材料满足了作为优秀光热试剂的要求。最后，血液学和组织学检查结果表明，在给定剂量下，SPNS和Pd@Au在大鼠和兔子中具有良好的生物相容性。我们希望这项工作能够推动二维钯基纳米材料向实际临床应用的发展，并为未来应用于更大动物肿瘤模型的其他治疗诊断纳米平台提供指导。