Wang Chunzhen, Li Jinghui, Liu Kehan, Li Junjin, Zhang Fan, Ma Xiaomin, Li Yuezheng, Zhang Chengmei, Liu Xiangdong, Qu Yuanyuan, Zhao Mingwen, Li Weifeng, Huang Weimin, Li Yong-Qiang
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China.
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300070, China.
ACS Nano. 2025 Jan 21;19(2):2922-2935. doi: 10.1021/acsnano.4c16766. Epub 2025 Jan 7.
Aplastic anemia (AA) is a life-threatening hematologic disease with limited therapeutic options. Stalled erythropoiesis and oxidative stress-induced hemocyte apoptosis are the main pathological features of AA, yet therapeutic agents that address these issues remain elusive. In this study, we report distinctive donkey-hide gelatin-derived carbon dots (G-CDs) that enable erythropoiesis activation and oxidative stress elimination to tackle refractory AA. We demonstrate that G-CDs can promote the proliferation and erythroid differentiation of hematopoietic stem cells as well as erythrocyte maturation, activating the whole process of erythropoiesis. Moreover, G-CDs display multienzyme-like activities and dramatically alleviate the oxidative stress of bone marrow and peripheral blood via catalytic scavenging of multiple reactive oxygen species, reconstructing the hematopoietic microenvironment. Intravenously or orally administered to AA mice induced by chemotherapy drugs, G-CDs significantly boost the level of red blood cells and hemoglobin and lead to the complete recovery of hematopoietic function, showing better therapeutic performance than clinically approved erythropoietin (EPO) without adverse effects. By collaboratively addressing the issues of stalled erythropoiesis and oxidative stress, the G-CDs-based intervention strategy may offer a powerful paradigm for clinical AA management.
再生障碍性贫血（AA）是一种危及生命的血液疾病，治疗选择有限。红细胞生成停滞和氧化应激诱导的血细胞凋亡是AA的主要病理特征，但解决这些问题的治疗药物仍然难以捉摸。在本研究中，我们报告了独特的阿胶衍生碳点（G-CDs），其能够激活红细胞生成并消除氧化应激以治疗难治性AA。我们证明，G-CDs可以促进造血干细胞的增殖和红系分化以及红细胞成熟，激活整个红细胞生成过程。此外，G-CDs表现出多酶样活性，并通过催化清除多种活性氧显著减轻骨髓和外周血的氧化应激，重建造血微环境。对化疗药物诱导的AA小鼠静脉内或口服给予G-CDs，可显著提高红细胞和血红蛋白水平，并导致造血功能完全恢复，显示出比临床批准的促红细胞生成素（EPO）更好的治疗性能且无不良反应。通过协同解决红细胞生成停滞和氧化应激问题，基于G-CDs的干预策略可能为临床AA管理提供有力范例。
