Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing, 211800, P. R. China.
Department of Chemistry, National University of Singapore, Singapore, 117543, Singapore.
Adv Mater. 2019 Nov;31(46):e1902791. doi: 10.1002/adma.201902791. Epub 2019 Sep 8.
Protein/antibody therapeutics have exhibited the advantages of high specificity and activity even at an extremely low concentration compared to small molecule drugs. However, they are accompanied by unfavorable physicochemical properties such as fragile tertiary structure, large molecular size, and poor penetration of the membrane, and thus the clinical use of protein drugs is hindered by inefficient delivery of proteins into the host cells. To overcome the challenges associated with protein therapeutics and enhance their biopharmaceutical applications, various protein-loaded nanocarriers with desired functions, such as lipid nanocapsules, polymeric nanoparticles, inorganic nanoparticles, and peptides, are developed. In this review, the different strategies for intracellular delivery of proteins are comprehensively summarized. Their designed routes, mechanisms of action, and potential therapeutics in live cells or in vivo are discussed in detail. Furthermore, the perspective on the new generation of delivery systems toward the emerging area of protein-based therapeutics is presented as well.
蛋白质/抗体疗法与小分子药物相比，即使在极低的浓度下也表现出高度的特异性和活性。然而，它们也伴随着不理想的物理化学性质，如脆弱的三级结构、较大的分子大小和较差的膜穿透性，因此蛋白质药物的临床应用受到蛋白质向宿主细胞内有效传递的阻碍。为了克服蛋白质治疗的挑战并增强其生物制药应用，开发了具有所需功能的各种蛋白质负载纳米载体，如脂质纳米胶囊、聚合物纳米颗粒、无机纳米颗粒和肽。在这篇综述中，全面总结了蛋白质的细胞内递药策略。详细讨论了它们的设计途径、作用机制以及在活细胞或体内的潜在治疗效果。此外，还介绍了新一代递药系统在新兴蛋白质治疗领域的应用前景。
