Deng Hong, Chen Jiayu, Wang Huimin, Liu Runmeng, Zhang Yiyi, Chang Hui, Tung Ching-Hsuan, Zhang Weiqi
State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China.
State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an 710069, PR China.
Carbohydr Polym. 2025 Mar 1;351:123123. doi: 10.1016/j.carbpol.2024.123123. Epub 2024 Dec 5.
Photodynamic therapy (PDT) eradicates tumor cells by the light-stimulated reactive oxygen species, which also induces lipid peroxidation (LPO) and subsequently ferroptosis, an iron-depended cell death. Ferroptosis has a tremendous therapeutic potential in cancer treatment, however, the ferroptosis efficiency is largely limited by the available iron in cells. Through hijacking the CD44-mediated iron endocytosis of hyaluronan (HA), here PDT with enhanced ferroptosis was realized by a HA@Ce6 nanogel self-assembled from HA, a photosensitizer Chlorin e6 (Ce6) and Fe as cross-linkers. Taking advantages of HA's natural affinity towards CD44, HA@Ce6 enabled a targeted Ce6 delivery in CD44-overexpressed breast cancer cells and meanwhile enhanced iron uptake to "fuel" ferroptosis together with the light-stimulated LPO. Further, HA@Ce6 demonstrated an excellent anticancer PDT efficacy and ferroptosis induction in the murine 4 T1 xenograft model. This HA@Ce6 successfully exploited the role of HA in iron transport to sensitize ferroptosis, providing a potent strategy to facilitate the anticancer PDT.
光动力疗法（PDT）通过光刺激产生的活性氧来清除肿瘤细胞，活性氧还会诱导脂质过氧化（LPO），随后引发铁死亡，这是一种铁依赖性细胞死亡。铁死亡在癌症治疗中具有巨大的治疗潜力，然而，铁死亡效率在很大程度上受到细胞内可用铁的限制。通过劫持透明质酸（HA）的CD44介导的铁内吞作用，由HA、光敏剂二氢卟吩e6（Ce6）和Fe作为交联剂自组装而成的HA@Ce6纳米凝胶实现了具有增强铁死亡作用的光动力疗法。利用HA对CD44的天然亲和力，HA@Ce6能够在CD44过表达的乳腺癌细胞中实现靶向Ce6递送，同时增强铁摄取，与光刺激的LPO一起为铁死亡“提供燃料”。此外，HA@Ce6在小鼠4T1异种移植模型中表现出优异的抗癌光动力疗法疗效和铁死亡诱导作用。这种HA@Ce6成功利用了HA在铁转运中的作用来使铁死亡敏感化，为促进抗癌光动力疗法提供了一种有效的策略。
