Here, the porosity of a metal organic framework (MIL-101) is tailored by the choice of the solvent occupying the pores in a template free acid etching process. Employing a slightly basic solvent such as DMF afforded big pores around 30 nm (BP-MIL-101). Catalase (CAT), which is a large protein (6 × 10 nm), was successfully encapsulated by a diffusion-based method with a high capacity of 12.5%. BP-MIL-101 could successfully protect CAT from both digestion and denaturation while maintaining its catalytic activity. This paves the way for encapsulating different large biological targets for eventual translation and delivery.