The exploration of metal-organic frameworks (MOFs) with good biocompatibility and physiological stability as carrier platforms for biomedical applications is of great importance but remains challenging. Herein, we developed an in situ biomimetic mineralization strategy on zeolitic imidazolate framework (ZIF) nanocrystals to construct a drug release system with favorable cytocompatibility, improved stability, and pH responsiveness. With lysozyme (Lys) wrapped on the surface of Zn-based ZIF (ZIF-8), Lys/ZIF-8 could strongly bond metal ions to promote nucleation and growth of bone-like hydroxyapatite (HAp), leading to formation of HAp@Lys/ZIF-8 composites. In vitro investigations indicate that the composites with a hollow Lys/ZIF-8 core and a HAp shell exhibited a high drug-loading efficiency (56.5%), smart pH-responsive drug delivery, cytocompatibility, and stability under physiological conditions. The proposed biomimetic mineralization strategy for designing MOFs-based composites may open a new avenue to construct advanced delivery systems in the biomedical field.
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