Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
State Key Laboratory of Bio-fibers and Eco-textiles, Shandong Collaborative Innovation Center of Marine Biobased Fibers and Ecological Textiles, Institute of Marine Biobased Materials, School of Environmental Science and Engineering, Qingdao University, Qingdao 266071, China.
ACS Appl Bio Mater. 2021 Apr 19;4(4):3499-3506. doi: 10.1021/acsabm.1c00036. Epub 2021 Mar 3.
One-dimensional (1D) nanomaterials are widely used in different fields, and the increased application of 1D nanomaterials has drawn concerns about their unknown toxicity. 1D titanium oxide (TiO) nanomaterials in different crystal phases are commonly applied in environmental remediation and solar energy conversion fields, but these materials pose a threat to human health, especially to the kidneys, an organ with abundant blood flow. To systematically evaluate the cytotoxicity to the kidneys, TiO nanofibers with TiO(B), anatase, and rutile phases, as well as nanorods with anatase and rutile phases were synthesized and added to the culture medium of HK2 cells. Cell counting kit-8 assay, 2',7'-dichlorofluorescin diacetate assay, Hoechst 33342 staining experiments, and quantitative real-time reverse transcription polymerase chain reaction tests were used to explore the renal effects of the as-prepared TiO nanomaterials in the short term or long term. In the short-term evaluation, all the added TiO nanomaterials were toxic to HK2 cells, and the cytotoxicity was dose-dependent. Rutile TiO can widely attach to the cell surface and displays the most serious cell-killing and proapoptotic ability, while anatase induces the most serious oxidative stress. In long-term evaluation, all the as-prepared TiO nanomaterials led to epithelial mesenchymal transition (EMT), a mechanism of renal fibrosis. Consistent with the short-term results, rutile induced the most serious EMT. This study indicated that the renal toxicity of 1D TiO nanomaterials is crystal phase-dependent and that rutile induced the most significant renal cell injury. Oxidative stress is a crucial but not the only contributor to the renal toxicity of TiO nanomaterials in the short term.
一维（1D）纳米材料在不同领域得到了广泛的应用，而 1D 纳米材料的广泛应用引起了人们对其未知毒性的关注。不同晶相的一维钛氧化物（TiO）纳米材料广泛应用于环境修复和太阳能转换领域，但这些材料对人类健康构成威胁，尤其是对富含血液的肾脏。为了系统地评估对肾脏的细胞毒性，合成了具有 TiO(B)、锐钛矿和金红石相的 TiO 纳米纤维以及具有锐钛矿和金红石相的纳米棒，并将其添加到 HK2 细胞的培养基中。使用细胞计数试剂盒-8 测定法、2'，7'-二氯荧光素二乙酸酯测定法、Hoechst 33342 染色实验和实时定量逆转录聚合酶链反应测试来探索短期或长期的制备的 TiO 纳米材料对肾脏的影响。在短期评价中，所有添加的 TiO 纳米材料对 HK2 细胞均有毒性，且细胞毒性呈剂量依赖性。金红石 TiO 可以广泛附着在细胞表面，并表现出最严重的细胞杀伤和促凋亡能力，而锐钛矿则引起最严重的氧化应激。在长期评价中，所有制备的 TiO 纳米材料均导致上皮间质转化（EMT），这是一种肾脏纤维化的机制。与短期结果一致，金红石诱导了最严重的 EMT。本研究表明，1D TiO 纳米材料的肾毒性与晶体相有关，金红石诱导了最显著的肾细胞损伤。氧化应激是 TiO 纳米材料短期肾毒性的关键因素，但不是唯一因素。
