非小细胞肺癌（NSCLC）是肺癌最常见的病理类型，约占肺癌的85%。在精准医疗和免疫治疗时代，铂基药物已经使用了40多年，仍然是最常用的抗癌药物之一。然而，铂基药物的临床限制，如严重的副作用和药物耐药性，尚未得到很好地解决。本研究基于Pt（IV）药物和纳米递送系统构建了一种新的白蛋白包裹的Pt（IV）纳米药物（HSA@Pt（IV））。纳米药物的表征和生物实验证明了其出色的药物输送和抗肿瘤效果。转录组和离子组的多组学分析揭示了纳米药物通过影响NSCLC细胞内铁离子稳态激活细胞死亡机制。本研究提供了HSA@Pt（IV）作为一种具有临床应用潜力的纳米药物的实验证据。© 2023 The Authors. Small published by Wiley-VCH GmbH.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)-based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt-based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin-encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi-omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application.© 2023 The Authors. Small published by Wiley-VCH GmbH.