Construction Of Porous Nanocomposites And Its Performance On Removal Of Protein-Bound Toxin

Excess indoxyl sulfate（IS）and bilirubin（BR）in the blood can not only aggravate chronic kidney disease（CKD）but also predispose to serious cardiovascular disease.Protein-bound toxins are mostly hydrophobic and are difficult to remove because they bind easily to human serum albumin（HSA）after entering the bloodstream.Kidney transplantation is an effective method to cure kidney disease,but there are a series of problems such as scarce donor,low success rate and high price.Therefore,blood purification techniques such as hemodialysis（HD）and hemoperfusion（HP）have become effective methods to treat uremia in clinical practice.Most of the porous adsorbents used in clinical practice,such as activated carbon,molecular sieve and adsorbent resin,have unsatisfactory adsorption performance and suffer from poor blood compatibility,chemical instability and high cost,which seriously limit the effectiveness of blood purification for toxin removal.Therefore,it is urgent to develop an efficient,safe and inexpensive adsorbent for blood purification.Herein,different porous nanocomposites were constructed and applied to HD and HP due to the analysis of the molecular structure and chemical composition of IS and BR.The morphological and structural characteristics of the adsorbent were explored to modulate the composition ratio of the composite.High performance protein-bound toxin adsorbents were developed and details of the study were as follows:1.The metal-organic frameworks material MIL-101（Cr）with ortho-octahedral structure were synthesized by high-temperature hydrothermal method using Chromium（III）nitrate（Cr（NO₃）₃·9H₂O）and terephthalic acid（H₂BDC）as raw materials.And the PAN-M60 nanofibrous composite membranes with 60 wt%MIL-101（Cr）loading were prepared by adjusting the amount of MIL-101（Cr）doping and using electrospinning method for hemodialysis to remove protein-bound toxins IS.The experimental results showed that MIL-101（Cr）nanoparticles and PAN-M60nanofibrous membranes reached the adsorption equilibrium at the initial IS concentration of 500mg/L,and the maximum adsorption amounts were 170 mg/g and 103 mg/g,respectively.The whole adsorption process was consistent with the Langmuir isotherm model.MIL-101（Cr）nanoparticles had an extremely fast adsorption rate,which could reach the adsorption equilibrium in less than 5min.The PAN-M60 nanofibrous membrane was also able to complete the adsorption in a relatively short time of 15 min,and the adsorption processes of both were in accordance with the pseudo-second-order kinetic model.When the PAN-M60 were placed in dialysate to simulate hemodialysis,the clearance rate of IS was increased from 35.4%to 61.1%at a volume of 200 m L of dialysate,which was comparable to that of 2000 m L of dialysate（62.5%）.Therefore,the efficient adsorption performance demonstrated by PAN-M60 could be used to regenerate dialysate for the purpose of miniaturizing conventional hemodialysis.2.KCC-1 mesoporous silica was synthesized using cetyltrimethylammonium bromide as the template agent and tetraethyl orthosilicate as the silica source,and NH₂-Si O₂ nanoparticles were obtained by immobilizing amino groups on the synthesized silica using a post-grafting method.NH₂-Si O₂ functional particles were wrapped with biocompatible polyethersulfone（PES）and freeze-dried to obtain NH₂-Si O₂/PES microbeads with a 75 wt%NH₂-Si O₂ loading.The equilibrium adsorption of Si O₂ on BR before and after grafting with amino groups was increased from 210 mg/g to 316 mg/g and the maximum adsorption amount of microbeads was 214 mg/g at the initial BR concentration of 400 mg/L,which was in accordance with the Langmuir isothermal model.The adsorption process was able to reach the adsorption equilibrium within 2 h and the adsorption kinetics was in accordance with the pseudo-second-order kinetic model.Moreover,the analysis of the adsorption mechanism showed that the adsorption of NH₂-Si O₂ on BR was mainly controlled by the electrostatic effect of amino and hydroxyl groups on mesoporous silica.The NH₂-Si O₂/PES composite beads showed a good adsorption performance and solved the problem of difficult recovery of the powder during use,which was expected to be used for efficient removal of protein-bound toxin BR by hemoperfusion.