Shi Jiangnan, Cui Guoqing, Jin Yaqi, Mi Boyu, Liu Kenan, Zhao Linqian, Bao Kewang, Lu Ziyao, Liu Jie, Wang Yuwei, He Hui, Guo Zhengqing
State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Adv Healthc Mater. 2024 Dec;13(31):e2402474. doi: 10.1002/adhm.202402474. Epub 2024 Oct 13.
Radiotherapy plays a crucial role in the treatment of advanced breast cancer, but the increased antioxidant system, especially the rise in glutathione (GSH), presents a significant obstacle to its effectiveness. To address this challenge, a versatile GSH-depleted photodynamic nanoadjuvant is developed to augment the efficacy of radiotherapy for breast cancer treatment. This nanoadjuvant operates within the tumor microenvironment to effectively deplete intracellular GSH through a sequence of cascaded processes, including GSH exhaustion, biosynthetic inhibition, and photodynamic oxidation. This leads to a notable accumulation of lipid peroxides (LPO) and subsequent suppression of glutathione peroxidase 4 (GPX4) activity. Consequently, the combined GSH depletion induced by the nanoadjuvant markedly promotes nonferrous ferroptosis, thereby contributing to the augmentation of antitumor efficiency during radiotherapy in breast cancer. This work presents an innovative approach to designing and synthesizing biocompatible nanoadjuvants with the goal of improving the efficacy of radiotherapy for breast cancer in prospective clinical scenarios.
放射疗法在晚期乳腺癌的治疗中起着关键作用，但抗氧化系统的增强，尤其是谷胱甘肽（GSH）的升高，对其疗效构成了重大障碍。为应对这一挑战，开发了一种多功能的GSH耗尽型光动力纳米佐剂，以增强放射疗法治疗乳腺癌的疗效。这种纳米佐剂在肿瘤微环境中发挥作用，通过一系列级联过程有效地耗尽细胞内的GSH，包括GSH耗竭、生物合成抑制和光动力氧化。这导致脂质过氧化物（LPO）显著积累，并随后抑制谷胱甘肽过氧化物酶4（GPX4）的活性。因此，纳米佐剂诱导的联合GSH耗尽显著促进了非铁性铁死亡，从而有助于在乳腺癌放疗期间提高抗肿瘤效率。这项工作提出了一种创新方法，用于设计和合成生物相容性纳米佐剂，旨在在前瞻性临床场景中提高乳腺癌放疗的疗效。
