State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha , 410082 , People's Republic of China.
J Am Chem Soc. 2018 Aug 8;140(31):9912-9920. doi: 10.1021/jacs.8b04457. Epub 2018 Jul 27.
Efficient delivery and endo-lysosomal release of active proteins in living cells remain a challenge in protein-based theranostics. We report a novel protein delivery platform using protein-encapsulating biomineralized metal-organic framework (MOF) nanoparticles (NPs). This platform introduces an adapted biomimetic mineralization method for facile synthesis of MOF NPs with high protein encapsulation efficiency and a new polymer coating strategy to confer the NPs with long-term stability. In vitro results show that protein-encapsulating MOF NPs have the advantages of preserving protein activity for months and protecting proteins from enzyme-mediated degradation. Live cell studies reveal that MOF NPs enable rapid cellular uptake, efficient release and escape of proteins from endo-lysosomes, and preservation of protein activity in living cells. Moreover, the developed platform is demonstrated to enable easy encapsulation of multiple proteins in single MOF NPs for efficient protein co-delivery. To our knowledge, it is the first time that protein-encapsulating MOF NPs have been developed as a generally applicable strategy for intracellular delivery of native active proteins. The developed protein-encapsulating biomineralized MOF NPs can provide a valuable platform for protein-based theranostic applications.
在活细胞中有效递送至内体-溶酶体并释放活性蛋白仍然是蛋白基治疗学中的一个挑战。我们报告了一种新型的蛋白质递药平台，该平台使用包封蛋白质的生物矿化金属-有机骨架（MOF）纳米颗粒（NPs）。该平台引入了一种适应性的仿生矿化方法，可简便合成具有高蛋白质包封效率的 MOF NPs，并采用新的聚合物涂层策略使 NPs 具有长期稳定性。体外实验结果表明，包封蛋白质的 MOF NPs 具有几个月内保持蛋白质活性和保护蛋白质免受酶介导的降解的优点。活细胞研究表明，MOF NPs 可实现蛋白质的快速细胞内化、有效从内体-溶酶体中释放和逃逸，并在活细胞中保持蛋白质活性。此外，所开发的平台被证明可以轻松地将多种蛋白质共包封于单个 MOF NPs 中，从而实现高效的蛋白质共递药。据我们所知，这是首次将包封蛋白质的 MOF NPs 开发为用于细胞内递送至天然活性蛋白质的通用策略。所开发的包封蛋白质的生物矿化 MOF NPs 可为蛋白基治疗应用提供有价值的平台。
