Thermoresponsive Self-Assembled β-Cyclodextrin-Modified Surface for Blood Purification

ACS Biomater Sci Eng. 2017 Jun 12;3(6):1083-1091. doi: 10.1021/acsbiomaterials.7b00156. Epub 2017 Apr 20.

Abstract

For patients with liver failure, bilirubin (BR) is one of the endogenous toxins in their blood. Although blood purification can remove the bilirubin from the body in clinics, the detoxification system needs to be improved, and the cost needs to be decreased. In the present study, we developed a recyclable model surface that can strongly remove bilirubin. We first prepared adamantane (Ad) on a model gold surface by self-assembly. Then, we integrated the β-cyclodextrin dimer (CDD) onto the surface with host-guest interactions between one of the CD cavities in the CDD and Ad. We characterized the surface with XPS, static contact angle measurements, and AFM. In addition, we employed QCM-D to characterize the preparation process as well as the detoxification of the surface. We demonstrated that this modified surface could strongly adsorb bilirubin through host-guest interactions between the CD cavities in the CDD and bilirubin and that the detoxification was improved 1.7 times (compared to the surface only with Ad). Interestingly, after characterization with QCM-D, this surface could be recycled due to the thermoresponsive property of the host-guest interaction between the CDD and Ad. After adsorbing the toxin and increasing the temperature to 45 °C, the CDD with bilirubin could be removed from the surface. Then, the refreshed surface with CDD could be prepared again at room temperature. This cycle could be repeated at least 3 times. Additionally, during each cycle, the modified surface exhibited good detoxification to bilirubin. This modified surface also showed strong resistance to plasma proteins, decreasing the adsorption of human serum albumin (HSA) and fibrinogen (Fg). An in vitro platelet adhesion assay showed that the adhesion of the platelets on the modified surface decreased and that the platelets were in an inactivated state. The hemolysis assay showed that this surface exhibited no hemolysis activity in the samples to red blood cells (RBCs). The CCK-8 assay showed that this surface had negligible cytotoxicity to L929 cells. This work has taken advantage of the host-guest self-assembly between β-CD and BR/Ad for special recognizing adsorption, as well as the thermoresponse of β-CD-Ad inclusion for recyclable application, and these results demonstrate that this technology has great potential for removing bilirubin and decreasing clinic costs.

Keywords: bilirubin; host−guest; self-assembly; thermoresponsive; β-cyclodextrin.