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Abstract Nano-ZIF-8 has gained extensive attention in the biomedical field in terms of its structural and functional advantages. However, these nanoparticles exhibit poor stability in physiological conditions and are particularly prone to the aggregation effect, which results in elevated local concentrations and affects the following degradation processes. The concentration and time regulation mechanism of ZIF-8 degradation remain incompletely elucidated in current research. Therefore, in this study, we investigate the effects of degradation concentration and duration on the degradation products of nano-ZIF-8 using phosphate-buffered saline as a simulated medium. Scanning electron microscopy, energy-dispersive x-ray spectroscopy, x-ray diffractometer, Fourier transform infrared spectrometer and x-ray photoelectron spectroscopy were applied to characterize the morphological, compositional, and structural evolution of the degradation products over time. The results revealed that the degradation of nano-ZIF-8 exhibited multi-stage transformation characteristics. After 4 weeks of degradation, the morphology and structure of the products exhibited an obvious concentration- and time-dependent behavior. At 5 mg ml −1 , the primary degradation mechanisms remain framework disintegration and ion reorganization. As the concentration increases, secondary crystallization and crystal reconstruction gradually emerged, leading to the formation of micron-sized reconstructed crystals, which mainly composed of immature ZIF-8 (truncated rhombic dodecahedron), dia(ZIF-8), NaZnPO 4 ·H 2 O and HMIM. Zebrafish assessment data showed that the biotoxicity of the degradation products was positively correlated with both concentration and incubation time. The products from the concentration of 20 and 30 mg ml −1 groups after 12 weeks of degradation demonstrated significant inhibitory effects on embryonic survival, hatching rate, and swim bladder development. It indicates that micron-sized crystals reconstructed during the process of high-concentration degradation are the key factor inducing biotoxicity. The results of the present investigation provide deeper insights into the biocompatibility of nano-ZIF-8, and supplies a theoretical rationale and guidance for its biomedical applications.
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