Metal-organic framework (MOF) is a type of emerging porous material that demonstrates promising potentials in energy, sensing, conversion, separation, and more recently, enzyme encapsulation. However, the research of enzyme-MOF composites mainly focuses on the synthetic strategy, and practical applications of enzyme-MOF composites have yet been mentioned in the literature. In this dissertation, the performance of enzyme-MOF composites in biomedical applications will be discussed in detail. The chemical stability of MOFs in aqueous solutions is a prerequisite for enzyme immobilization. Bearing this in mind, a novel reductive labilization strategy for the preparation of an ultrastable Cr(III)-MOF from Fe(III)-MOF is discovered, which might be useful for the improvement of material stability in aqueous media. The resulting Cr(III)-MOF shows much broader pH tolerance in aqueous solutions and can be used to incorporate polyethylenimine (PEI) for carbon dioxide capture. Most of the current enzyme-MOF composites only carry single enzymatic function, while multi-enzyme immobilized materials may be superior in complex systems. To achieve this goal, a novel mesoporous MOF, PCN-888, is rationally designed to accommodate two enzymes, glucose oxidase (GOx) and horseradish peroxidase (HRP), via a stepwise encapsulation manner. This bienzymatic MOF nanoreactor persists enzymatic activities very well and is resistant to trypsin digestion. Based on the above-mentioned stepwise encapsulation strategy, a nanoscale bienzymatic nanofactory is prepared based on PCN-333. This nanofactory can be endocytosed by living cells, accumulated in lysosomes, and exert protective effect to cells against oxidative damage. More importantly, because of the preservation of enzyme structure and function by the MOF material, the enzymatic activity of enzyme-MOF nanofactory can last as long as one week after the nanofactory is internalized. Inspired by the long-lasting performances of enzyme-PCN-333 nanofactory, a therapeutic enzyme-PCN-333 nanoreactor is developed to activate a nontoxic prodrug in cancer cells. In this case, tyrosinase (TYR) is encapsulated and can convert innocent paracetamol to cytotoxic o-quinone species in cancer cells. This prodrug activation process can effectively kill multiple types of cancer cells, including a drug resistant cell line. The effectiveness of this strategy is further proved on in vivo models bearing human tumor xenograft.
