Liu Gaojian, Wen Wenjing, Zhao Xuan, Jing Yanan, Li Hao, Fan Xulong, Huang ZiXuan, Liang Gaofeng
School of Basic Medicine and Forensic Medicine, Henan Engineering Center of Micronano materials and Precise Theranostics in Tumors, Henan University of Science & Technology, Luoyang 471023, People's Republic of China.
Institute of Organoids on Chips Translational Research, Henan Academy of Sciences, Zhengzhou 450046, People's Republic of China.
Nanotechnology. 2025 Jul 23;36(30). doi: 10.1088/1361-6528/ade1de.
Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol-maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional 'natural' nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.
乳腺癌是全球女性中最常见的致命癌症，也是女性死亡的主要原因。铁死亡是一种程序性细胞死亡形式，依赖于铁且非凋亡性，由细胞抗氧化系统的抑制引发。光动力疗法（PDT）利用光敏剂产生活性氧（ROS），增加肿瘤细胞中的氧化应激。当与铁死亡结合时，PDT可协同作用以调节细胞内氧化还原平衡。在本研究中，我们设计了工程化纳米红细胞膜用于靶向递送氯e6（Ce6）和顺铂（DDP）以增强乳腺癌治疗。通过使用温和超声，将Ce6和DDP共负载到纳米红细胞膜上，结合铁死亡诱导剂和光敏剂来对抗乳腺癌。为了提高对乳腺癌的靶向能力，通过硫醇-马来酰亚胺偶联反应将RGD环肽修饰到纳米红细胞膜上。共负载Ce6和DDP的RGD修饰纳米红细胞膜不仅继承了红细胞膜良好的稳定性和显著的生物相容性，还促进了乳腺癌细胞的摄取，有效诱导这些细胞发生铁死亡。总之，这种多功能“天然”纳米药物递送系统为PDT联合铁死亡治疗乳腺癌提供了一种有效且安全的方法。
