Assessing the colloidal stability of copper doped ZIF-8 in water and serum

Abstract

Colloidal formulations to treat cardiovascular conditions are urgently needed since diseases like atherosclerosis are a major societal burden and agonizing for affected individuals. Copper ions and zinc ions as well as correctly dosed nitric oxide (NO) have long been known to alleviate these pathologies. Herein, we present strategies for size-controlled crystallization of copper-doped Zeolitic Imidazolate Framework 8 (ZIF-8). The colloidal stability and structural integrity of copper-doped ZIF-8 was assessed in water and blood serum. Key findings of the present study include that structural integrity of colloidal copper doped ZIF-8 in blood serum is maintained over several days, while disintegration occurs more quickly in water. Further, we confirmed the known ability of copper-doped ZIF-8 micro-particles to convert blood borne s-nitrosothiols into nitric oxide for the presented colloidal formulations. Nitric Oxide conversion was more moderate and sustained in colloidal copper-doped ZIF-8 formulations compared to free copper ions in solution, which is crucial for many biomedical applications. Another key finding of the present study is that the onset of rapid structural disintegration of copper-doped ZIF-8 occurs at pH 5.5, which is a common physiological pH regime of atherosclerotic plaques. Colloidal particles are known to accumulate in atherosclerotic plaques and the presented system may be a valuable addition to the emerging field of nanomedicines for atherosclerosis treatment. The present study has evaluated the colloidal stability and structural integrity, establishing required material characteristics needed for biological evaluation of the material in future dedicated studies.