Since its discovery in 1978, cisplatin-based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin-induced acute kidney injury (AKI), which occurs in 30% of cisplatin-treated patients. Unfortunately, no effective solution for preventing or managing this severe complication, which greatly impacts its clinical administration. Kidney is the main organ injured by cisplatin, and the injury is related to cisplatin-induced cell apoptosis and DNA injury. Therefore, to achieve the safe use of cisplatin in tumour treatment, the key lies in identifying a kidney treatment that can effectively minimize cisplatin nephrotoxicity. Here, we successfully synthesized and applied a DNA-nanostructure complex, named TFG, which contains tetrahedral framework nucleic acids (tFNAs) and FG-4592, a novel Hif-1α inducer. As cargo, TFG is composed entirely of DNA strands. It possesses low nephrotoxicity and renal aggregation properties while FG-4592 is able to relieve renal injury by downregulating the apoptosis signal pathways. And it can relieve cisplatin-induced renal injury when taken cisplatin treatment. This work aims to enhance chemotherapy protection in tumour patients by using TFG, a DNA-based nanomedicines to kidney. This work has the potential to revolutionize the treatment of renal diseases, particularly drug-induced kidney injury, leading to improved clinical outcomes.

中文翻译：

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DNA纳米结构-Hif-1α诱导复合物作为对抗顺铂诱导的急性肾损伤的新型纳米疗法

自 1978 年发现以来，基于顺铂的化疗方案在人类癌症治疗中发挥了关键作用，挽救了数百万人的生命。然而，其高风险仍然对顺铂引起的急性肾损伤（AKI）构成重大挑战，30%的顺铂治疗患者会发生这种情况。不幸的是，没有有效的解决方案来预防或管理这种严重的并发症，这极大地影响了其临床治疗。肾脏是顺铂损伤的主要器官，其损伤与顺铂诱导的细胞凋亡和DNA损伤有关。因此，要实现顺铂在肿瘤治疗中的安全使用，关键在于找到一种能够有效降低顺铂肾毒性的肾脏治疗方法。在这里，我们成功合成并应用了一种DNA-纳米结构复合物，命名为TFG，其中含有四面体框架核酸（tFNA）和新型Hif-1α诱导剂FG-4592。作为货物，TFG 完全由 DNA 链组成。它具有低肾毒性和肾聚集特性，而 FG-4592 能够通过下调细胞凋亡信号通路来减轻肾损伤。顺铂治疗时可减轻顺铂引起的肾损伤。这项工作旨在通过使用基于 DNA 的肾脏纳米药物 TFG 来增强肿瘤患者的化疗保护。这项工作有可能彻底改变肾脏疾病的治疗，特别是药物性肾损伤，从而改善临床结果。