Inspired by natural biomineralization processes, a simple and universal strategy is introduced to construct a biomimetic nanoplatform for systemic codelivery of a nucleic acid therapeutic (G3139) and a chemotherapeutic drug doxorubicin (DOX). This codelivery system was synthesized through one-pot supramolecular self-assembly of G3139, DOX, and FeII ions through multiple coordination interactions, followed by an adapted surface mineralization with metal-organic frameworks. The resulting core-shell nanoparticles have uniform size, well-defined nanosphere structure, robust colloidal stability, ultrahigh drug loading efficiency and capacity, and precisely adjustable ratios of two therapeutic agents. The system can efficiently accumulate in the tumor, allowing for sensitive MRI detection and synergistical inhibition of tumor growth without apparent systemic toxicity.