A Novel Cascade Nanoreactor Integrating Two‐Dimensional Pd‐Ru Nanozyme, Uricase and Red Blood Cell Membrane for Highly Efficient Hyperuricemia Treatment

Abstract

hypertension, diabetes, kidney stones, and cardiovascular diseases. [5][6][7][8] Especially, hyperuricemia promotes the development of gout in which monosodium urate crystals are deposited in joints and peripheral tissues to result in acute and chronic inflammatory arthritis. [7] Although some drugs, like allopurinol and febuxostat, have been utilized for the treatment of hyperuricemia and gout, they can only alleviate the symptoms rather than fundamentally cure the hyperuricemia due to their lack of the capability to dissolve and eliminate existing UA. [9][10][11][12][13] Uricase, as a therapeutic enzyme, can lower the plasma UA level by catalyzing the conversion of UA to allantoin and H 2 O 2 , thus uricasebased UA degradation medications, such as recombinant uricase (rasburicase) and PEGylated recombinant uricase (pegloticase), have been approved for the clinical treatment of hyperuricemia and related diseases. [10,[14][15][16][17][18][19][20][21] However, more extensive application of uricase in clinic has been hindered by drawbacks such as vulnerable activities against environments, low catalytic activity and overproduction of pro-inflammatory hydrogen peroxide (H 2 O 2 ), which lead to limited therapeutic effect and undesirable side effects. [22][23][24][25][26] Therefore, there is an urgent need to develop novel enzyme delivery systems, with enhanced stabilities, long blood-circulation, good therapeutic efficacy and meanwhile reducing unwanted side effects, for hyperuricemia therapy.Recently, nanozymes, as alternatives to natural enzymes, have drawn tremendous attention for applications in biosensing, imaging, therapy, and environmental protection due to their higher stabilities, easier storage, lower costs and adjustable catalytic activities compared with the natural counterparts. [27][28][29][30][31][32][33][34][35] Especially, nanozymes as nanomaterials not only display the intrinsic enzyme-like activities, producing or excluding reactive oxygen species (ROS), but also can be combined with enzymes for cascade catalysis. [11,[36][37][38][39][40][41][42] For example, by integrating glucose oxidase (GOx) and ultrasmall Fe 3 O 4 nanozyme into the dendritic silica nanoparticles (NPs), Shi and coworkers fabricated a sequential nanocatalyst, in which GOx could effectively catalyze glucose in tumor cells into abundant H 2 O 2 , and the elevated H 2 O 2 was then catalyzed by the Fe 3 O 4 NPs via Nanozyme-based cascade reaction has emerged as an effective strategy for disease treatment because of its high efficiency and low side effects. Herein, a new and highly active two-dimensional Pd-Ru nanozyme is prepared and then integrated with uricase and red blood cell (RBC) membrane to fabricate a tandem nanoreactor, Pd-Ru/Uricase@RBC, for hyperuricemia treatment. The designed Pd-Ru/Uricase@RBC nanoreactor displayed not only good stability against extreme pH, temperature and proteolytic degradation, but also long circulation half-life and excellent safety. The nanoreactor can effectively degrade UA by uricase to allant...

Fully‐Exposed Pd Cluster Catalyst: An Excellent Catalytic Antibacterial Nanomaterial

“…At present, nanozymes have attracted extensive attention of the researchers. [4][5][6][7][8][9] The nanocomposites with different structures have been studied as nanozymes, such as metal nanoparticle nanozymes, [10][11][12] metal alloy nanozymes, [13][14][15] and single-atom nanozymes. [16][17][18] Among these nanozymes, the single-atom nanozymes have become a research hotspot as their highly efficient and diverse enzymes-like catalytic activities.…”

Injectable Hydrogel Based on Defect‐Rich Multi‐Nanozymes for Diabetic Wound Healing via an Oxygen Self‐Supplying Cascade Reaction

“…CAT‐like activity was evaluated by monitoring the generation of O 2 by the catalytic decomposition of H 2 O 2 . [ 47,48 ] As shown in Figure 4f,g, MoS 2 @Au@BSA and MoS 2 @Au NSs generated significantly higher levels of O 2 compared to the other groups; therefore, H 2 O 2 depletion was greatest with these materials, indicating remarkable CAT‐like activity. MoS 2 @Au@BSA exhibited the highest scavenging activity against the three representative ROS, and the final products of the antioxidant system were H 2 O and O 2 (Figure 4h).…”

Insulated expression of periplasmic uricase inE. coliNissle 1917 for the treatment of hyperuricemia

“…In addition to traditional urate-lowering chemical drugs, enzymes related to the degradation of urate are gaining attention, and may serve as a more direct method for hyperuricemia treatment 48,49 . Clinical data have shown that modified uricases, such as pegolase, lablipase, and pregabalin, display excellent performance in the treatment of intractable gout disease by intravenous injection; however, their duration of action in vivo is limited.…”