Cui Jian, Wang Keqing, Wu Zheyu, Sun Wei, Gao Tian, Shen Xiaochen, Wang Wei, Cao Yi, Xue Bin
Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China.
China Tobacco Jiangsu Industrial Co. Ltd., Nanjing 210019, China.
ACS Appl Mater Interfaces. 2025 Aug 27. doi: 10.1021/acsami.5c10918.
Protein-based nanoparticles (PNPs) represent a versatile and promising class of nanocarriers for biomedical applications, offering inherent biocompatibility, biodegradability, and functional adaptability. By leveraging the diverse structural and chemical characteristics of natural and engineered proteins, certain PNP systems have demonstrated the potential to achieve precise control over drug loading, release kinetics, and targeting under specific design strategies, making them attractive platforms for therapeutic and diagnostic delivery. In this review, we aim to provide a comprehensive understanding of the design of protein-based nanoparticles and their clinical translation by conducting an in-depth analysis of recent studies on protein nanoparticles, in conjunction with protein-related formulations approved by the FDA in the past five years. We outline the biological rationale for their use and examine key challenges─including stability, immunogenicity, and manufacturing scalability─that impact their clinical translation. Design strategies such as surface modification, ligand targeting, modularity, stimuli-responsive engineering, and computational approaches are highlighted for their role in overcoming these barriers and enhancing performance. We further explore applications across neurological disorders, cancer, infectious diseases, and diagnostics, illustrating the broad potential of these systems. Finally, we provide an in-depth analysis of the clinical landscape and manufacturing challenges of protein-based therapeutics, highlighting the potential of emerging in vivo gene and protein editing technologies to accelerate the development of innovative protein drugs with the aim of facilitating the clinical translation of PNPs. By synthesizing insights from materials science, biology, and medicine, this Perspective aims to guide the rational design of next-generation PNPs for effective and personalized healthcare solutions.
基于蛋白质的纳米颗粒（PNPs）是一类用于生物医学应用的多功能且前景广阔的纳米载体，具有固有的生物相容性、生物可降解性和功能适应性。通过利用天然和工程蛋白质的多样结构和化学特性，某些PNP系统已展现出在特定设计策略下实现对药物负载、释放动力学和靶向进行精确控制的潜力，使其成为治疗和诊断递送的有吸引力的平台。在本综述中，我们旨在通过深入分析近期关于蛋白质纳米颗粒的研究，并结合过去五年中美国食品药品监督管理局（FDA）批准的与蛋白质相关的制剂，全面了解基于蛋白质的纳米颗粒的设计及其临床转化情况。我们概述了其使用的生物学原理，并审视了影响其临床转化的关键挑战，包括稳定性、免疫原性和制造可扩展性。重点介绍了诸如表面修饰、配体靶向、模块化、刺激响应工程和计算方法等设计策略在克服这些障碍和提高性能方面的作用。我们进一步探讨了其在神经疾病、癌症、传染病和诊断方面的应用，阐明了这些系统的广泛潜力。最后，我们对基于蛋白质的治疗药物的临床现状和制造挑战进行了深入分析，强调了新兴的体内基因和蛋白质编辑技术在加速创新蛋白质药物开发方面的潜力，旨在促进PNP的临床转化。通过综合材料科学、生物学和医学的见解，本观点旨在指导下一代PNP的合理设计，以实现有效和个性化的医疗保健解决方案。
