Controlling interior of solid state materials to create various forms, such as core-shell, hollow, matryoshka, york-shell, and multi-shell hollow particles, has been an important challenge for synthetic chemists. In this presentation, we show a synthetic strategy to synthesize single-crystalline double-shell hollow metal-organic framework (MOF) crystals via sequential self-assembly. Such examples of extreme self-assembly might open up new avenues to various forms of MOFs for synthesizing single crystalline multi-shelled hollow MOF with hierarchical porous materials with trimodal (for example, micro-/meso-/macro porous structures) pore system. Further, MOF chemists can design biomimetic catalytic systems similar to native pyruvate dehydrogenase, composed of three different enzymes that are distributed individually in two shells, using the concept of the spatial separation presented here.