Histidine-Rich Protein Accelerates the Biomineralization of Zeolitic Imidazolate Frameworks for In Vivo Protein Delivery.

Biomineralization of metal-organic frameworks (MOFs) provides a powerful approach for intracellular protein delivery, enabling the study of biological function and therapeutic potential of proteins. However, the potency of this approach is largely challenged by the low efficiency of current strategies for interfacing proteins with MOFs for biomineralization and intracellular delivery. Here, we report a versatile and convenient biomineralization strategy for the rapid encapsulation and enhanced delivery of proteins using MOFs, accelerated by histidine-rich proteins. We demonstrate that the histidine-rich green fluorescent protein (H 39 GFP) can accelerate the biomineralization of MOFs by promoting the coordination between proteins and metal ions, leading to enhanced protein delivery efficiency up to 15-fold. Moreover, we show that the delivery of H 39 GFP-fused cytotoxic ribonuclease and bacterial-derived RAS protease can effectively inhibit tumor cell growth. The strategy of promoting the biomineralization of MOFs via histidine-rich proteins for enhanced intracellular delivery could be expanded to other biomacromolecules, advancing their therapeutic potential and the biomedical scope of MOFs.