Wang Yinxin, Shi Lei, Zou Chengzhi, Liu Zizhong, Wang Jia
The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, PR China.
Nanoscale. 2025 Jul 31;17(30):17428-17442. doi: 10.1039/d5nr01369k.
Ferritin is an iron-storage protein that naturally self-assembles into a hollow spherical particle consisting of 24 identical subunits, and it serves a central role in iron metabolism. Ferritin's favorable drug-loading capacity, biocompatibility, intrinsic targeting ability (, transferrin receptor 1 (TfR1)), and reversible self-assembly make it a promising nanoplatform for various applications, including drug delivery, targeted imaging, environmental remediation, and nanocatalysis. To overcome the limitations of native ferritin and expand its functional repertoire, researchers have employed strategies such as chemical modification, genetic engineering, and biomimetic mineralization. In particular, chemical modification approaches enable conjugation of targeting ligands, fluorescent probes, or polymer coating onto the ferritin surface, which can prolong the circulation time and improve delivery efficiency. Site-directed mutagenesis and fusion protein strategies enhance its stability and specificity while biomimetic mineralization utilizes the inner cavity of ferritin to synthesize metal nanoparticles and construct multifunctional composites. These advancements significantly broaden the scope of ferritin applications with great potential in precision medicine, treatment of neurodegenerative diseases, and biocatalysis. Yet, challenges remain regarding biosafety, scalable preparation, and clinical translation. Future research needs to focus on optimizing modification strategies to improve the stability and targeting efficiency of nano-delivery systems, and integrate new technologies such as artificial intelligence and synthetic biology to construct efficient, low toxicity and multifunctional nano-delivery systems. This review systematically summarizes the progress on ferritin nanoparticles, focusing on their structural characteristics, the potential of their native properties, and key modification strategies to enhance their functionality. We discuss their diverse biomedical applications, providing theoretical and technical references for related research and promoting the development of precision nanomedicine.
铁蛋白是一种铁储存蛋白，它能自然地自组装成一个由24个相同亚基组成的空心球形颗粒，在铁代谢中起核心作用。铁蛋白具有良好的药物负载能力、生物相容性、内在靶向能力（转铁蛋白受体1（TfR1））以及可逆自组装特性，使其成为用于各种应用的有前景的纳米平台，包括药物递送、靶向成像、环境修复和纳米催化。为了克服天然铁蛋白的局限性并扩展其功能范围，研究人员采用了化学修饰、基因工程和仿生矿化等策略。特别是，化学修饰方法能够将靶向配体、荧光探针或聚合物涂层连接到铁蛋白表面，这可以延长循环时间并提高递送效率。定点诱变和融合蛋白策略增强了其稳定性和特异性，而仿生矿化则利用铁蛋白的内腔合成金属纳米颗粒并构建多功能复合材料。这些进展显著拓宽了铁蛋白的应用范围，在精准医学、神经退行性疾病治疗和生物催化方面具有巨大潜力。然而，在生物安全性、可扩展制备和临床转化方面仍存在挑战。未来的研究需要专注于优化修饰策略，以提高纳米递送系统的稳定性和靶向效率，并整合人工智能和合成生物学等新技术，构建高效、低毒和多功能的纳米递送系统。本综述系统地总结了铁蛋白纳米颗粒的研究进展，重点关注其结构特征、天然特性的潜力以及增强其功能的关键修饰策略。我们讨论了它们多样的生物医学应用，为相关研究提供理论和技术参考，促进精准纳米医学的发展。
