Enzyme immobilization is a suitable strategy to promote biosensing, biocatalysis and the industrial applications of biomacromolecules. Although considerable efforts have been devoted to the construction of metal-organic frameworks (MOFs)-based porous nano-reactors, their enzymolysis efficiency cannot be tuned by varying the external conditions due to the fixed conformation of the encapsulated enzymes. In this work, a controllable embedding protocol was developed based on the concept of stimuli-responsive polymer modified MOFs. Using MOFs as a rigid template for thermo-responsive polymer modification and consequently utilizing the polymer-MOFs complexes for enzyme (glucose oxidase, horseradish peroxidase, trypsin, cytochrome c, glutaminase) immobilization, different porous nano-reactors were fabricated. Most importantly, the polymer on the MOF surface exhibited good ability to form a "soft nest" at high temperature for inducing the confinement effect and further improving the enzymolysis efficiencies of the nano-reactors 3.75-37.7-fold. Moreover, a colorimetric sensing method was developed to detect serum glucose with the proposed nano-reactors. This strategy is highly versatile and suitable for diverse rigid MOFs modified with stimuli-responsive soft-polymer-nests and enzymes.