Defects within the nanoscale UiO-66 metal–organic framework (MOF) are created to lock a hybrid phosphonoacetate ligand through Zr–O–P linkages, leaving the carboxyl group free to anchor cisplatin prodrug cis, cis, trans-[Pt(NH₃)₂Cl₂(OH)₂]. A drug loading of 256.5 mg g⁻¹ (25.7 wt% based on cisplatin) was achieved with a Zr₆ : Pt : P ratio of 1.5 : 1 : 1, which surpasses defect-free UiO-66 and several other MOF carriers. This framework exhibited a burst release of its payload in PBS solution in the first 2 h, releasing 71% of the drug, including a 50% payload release in less than 1 h. This work demonstrates that MOF defects can be intentionally engineered to achieve a high drug loading, and serves as an alternative to drug encapsulation using the pore void and through the association of the functionalized ligand.