UV-activated “blue bulbs” for photodecomposition and adsorption of bilirubin: Strategic nanoarchitectonics to remove protein-bound toxins

Abstract

Massive loss of proteins is common in patients on long-term blood purification therapy, there is a strong inverse association between the risk of death and serum albumin concentration. Removing toxins and leaving behind albumin is an arduous task in the field of blood purification. Inspired by the dissociation-transportation process of protein-bound toxins in renal tubule, we propose multi-point photodecomposition accompany with adsorption strategy as a novel treatment modality in hemoperfusion. As a proof of concept, bilirubin is chosen as the research object since it is a typical protein-bound toxin that needs to be transported by strong binding to albumin in blood environment. Interestingly, blue light can efficiently break bilirubin into some highly polar water soluble diazo compounds, the decomposed products of bilirubin are water-soluble and loosely bound to albumin. Herein, graphene quantum dots (GQDs) and polymer science are combined in the nanoarchitectonics processes. The “photodecomposition-adsorption” platform is designed by embedding GQDs in poly (diallyldimethylammonium chloride-acrylamide) (poly (DDAC-AAm) hydrogel (PDMG) microspheres. In order to reduce the influence of cationic polymer on blood component, hyaluronic acid (HA) are coated on the surface of the PDMG (PDMG@HA) microspheres by electrostatic interaction. Owing to the luminescence property of GQDs, the PDMG@HA microspheres emit blue light under ultraviolet activation and decompose bilirubin into water soluble diazo compounds, just like numerous “blue bulbs”. The water-soluble bilirubin debris could be dissociated from albumin and adsorbed by “blue bulbs”, which greatly reduce the metabolic burden on the body. In vitro biocompatibility results demonstrate that the PDMG@HA microspheres show lower protein adsorption and blood cell toxicity than the PDMG microspheres. The photodecomposition and adsorption amount of bilirubin is 187.8 mg/g in vitro. In hyperbilirubinemia rabbit hemoperfusion, the “blue bulbs” remove 70.9 % total bilirubin (TBIL) from plasma and defer the liver damage of biliary obstruction. Notably, the bilirubin photodecomposition is persisted to the end of the treatment, and some of the bilirubin debris have been adsorbed by the “blue bulbs”. The strategy combining both photodecomposition and adsorption opens a new route for the treatment of blood-related diseases.