Bae Chaewon, Kim Hyerim, Kook Yun-Min, Lee Chaedong, Kim Changheon, Yang Chungmo, Park Min Hee, Piao Yuanzhe, Koh Won-Gun, Lee Kangwon
Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
Mater Today Bio. 2022 Oct 14;17:100457. doi: 10.1016/j.mtbio.2022.100457. eCollection 2022 Dec 15.
Ferroptosis, a cell death pathway that is induced in response to iron, has recently attracted remarkable attention given its emerging therapeutic potential in cancer cells. The need for a promising modality to improve chemotherapy's efficacy through this pathway has been urgent in recent years, and this non-apoptotic cell death pathway accumulates reactive oxygen species (ROS) and is subsequently involved in lipid peroxidation. Here, we report cancer-targeting nanoparticles that possess highly efficient cancer-targeting ability and minimal systemic toxicity, thereby leading to ferroptosis. To overcome the limit of actual clinical application, which is the ultimate goal due to safety issues, we designed safe nanoparticles that can be applied clinically. Nanoparticles containing ferroptosis-dependent iron and FDA-approved hyaluronic acid (FHA NPs) are fabricated by controlling physicochemical properties, and the FHA NPs specifically induce ROS production and lipid peroxidation in cancer cells without affecting normal cells. The excellent anti-tumor therapeutic effect of FHA NPs was confirmed in the A549 tumor-bearing mice model, indicating that the induction of FHA NP-mediated cell death via the ferroptosis pathway could serve as a powerful platform in anticancer therapy. We believe that this newly proposed FHA NP-induced ferroptosis strategy is a promising system that offers the potential for efficient cancer treatment and provides insight into the safe design of nanomedicines for clinical applications.
铁死亡是一种因铁而诱导的细胞死亡途径，鉴于其在癌细胞中展现出的新兴治疗潜力，最近受到了显著关注。近年来，迫切需要一种有前景的方法来通过该途径提高化疗疗效，这种非凋亡性细胞死亡途径会积累活性氧（ROS），随后参与脂质过氧化。在此，我们报道了具有高效癌症靶向能力和最小全身毒性从而导致铁死亡的癌症靶向纳米颗粒。为了克服实际临床应用的限制（由于安全问题，这是最终目标），我们设计了可临床应用的安全纳米颗粒。通过控制物理化学性质制备了含有铁死亡依赖性铁和美国食品药品监督管理局（FDA）批准的透明质酸的纳米颗粒（FHA NPs），FHA NPs能在不影响正常细胞的情况下特异性地诱导癌细胞产生ROS和脂质过氧化。在A549荷瘤小鼠模型中证实了FHA NPs具有出色的抗肿瘤治疗效果，这表明通过铁死亡途径诱导FHA NP介导的细胞死亡可成为抗癌治疗的有力平台。我们相信，这种新提出的FHA NP诱导铁死亡策略是一个有前景的系统，具有高效治疗癌症的潜力，并为临床应用的纳米药物安全设计提供了思路。
