Metal-organic frameworks (MOFs) are promising multifunctional porous materials for biomedical and environmental applications. Here, we report synthesis and characterization of a new MOF based on the tetrahedral secondary building unit Zn O(CBAB) (NUIG4), where CBABH = 4-((4-carboxybenzylidene)amino)benzoic acid. NUIG4 belongs to the family of MOFs with primitive cubic pcu topology, being a rare example with 4-fold interpenetration. The pore architecture enables unprecedentedly high doxorubicin (DOX) loading capacity (1955 mg DOX/g NUIG4) with pH-controlled release. Solid-state NMR and modeling confirmed formation of aromatic π-π stacking interactions between DOX and the framework. Preliminary cell-line experiments suggested a protective effect of NUIG4 on healthy HDF cells against DOX toxicity. NUIG4 also displays potential for adsorptive small-molecule gas separation, with a BET surface area of 1358 m g and high selectivity of 2.75 for C H over CO .