Understanding the Adsorption and Diffusion Behaviors of PBUT in Biocompatible MOFs.

With the increasing incidence of chronic kidney disease, the effective control of protein-bound uremic toxins (PBUTs), which are difficult to remove through dialysis, has become a priority. In this study, the adsorption and diffusion behaviors of several metal-organic frameworks (MOFs) for PBUTs (indoxyl sulfate and p-cresyl sulfate) were studied by molecular dynamics (MD) simulations and umbrella sampling. For the NU series of MOFs, good correlations between the Gibbs free energy (ΔG) and the experimental clearance rates of PBUTs are found. For the adsorption behaviors, in terms of ΔG, DAJWET exhibits the best adsorption effect for indoxyl sulfate (IS), whereas NU-1000 shows the best effect for p-cresyl sulfate (pCS). Similar trends observed in the radial distribution function and mean square displacement results suggest that the π-π stacking interactions play a crucial role in the adsorption and diffusion of PBUTs by MOFs. Furthermore, it can be concluded that MOFs with highly conjugated groups (porphyrin rings and pyrene groups) tend to generate more PBUT attraction, and provide design principles for potential MOF candidates in the removal of PBUTs.

Albumin-manganese dioxide nanocomposites: a potent inhibitor and ROS scavenger against Alzheimer's ß-amyloid fibrillogenesis and neuroinflammation.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease pathologically caused by amyloid-ß protein (Aß) aggregation, oxidative stress, and neuroinflammation. The pathogenesis of AD is still uncertain and intricate, and helpful therapy has rarely been recorded. So, discovering amyloid modulators is deemed a promising avenue for preventing and treating AD. In this study, human serum albumin (HSA), a protein-based Aß inhibitor, was utilized as a template to guide the synthesis of HSA-manganese dioxide nanocomposites (HMn NCs) through biomineralization. The in situ formed MnO2 in HSA endows this nano-platform with outstanding reactive oxygen species (ROS) scavenging capability, including superoxide dismutase-mimetic and catalase-mimetic activities, which could scavenge the plethora of superoxide anion radicals and hydrogen peroxide. More importantly, the HMn NCs show enhanced potency in suppressing Aß fibrillization compared with HSA, which further alleviates Aß-mediated SH-SY5Y neurotoxicity by scavenging excessive ROS. Moreover, it is demonstrated that HMn NCs reduce Aß-related inflammation in BV-2 cells by lowering tumor necrosis factor-α and interleukin-6. Furthermore, transgenic C. elegans studies showed that HMn NCs could remove Aß plaques, reduce ROS in CL2006 worms, and promote the lifespan extension of worms. Thus, HMn NCs provide a promising tactic to facilitate the application of multifunctional nanocomposites in AD treatment.

Coassembled Chitosan-Hyaluronic Acid Nanoparticles as a Theranostic Agent Targeting Alzheimer's ß-Amyloid.

ß-Amyloid (Aß) fibrillogenesis is closely associated with the pathogenesis of Alzheimer's disease (AD), so detection and inhibition of Aß aggregation are of significance for the theranostics of AD. In this work, the coassembled nanoparticles of chitosan and hyaluronic acid cross-linked with glutaraldehyde (CHG NPs) were found to work as a theranostic agent for imaging/probing and inhibition of Aß fibrillization both in vitro and in vivo. The biomass-based CHG NPs of high stability exhibited a wide range of excitation/emission wavelengths and showed binding affinity toward Aß aggregates, especially for soluble Aß oligomers. CHG NPs displayed weak emission in the monodispersed state, while they remarkably emitted increased red fluorescence upon interacting with Aß oligomers and fibrils, showing high sensitivity with a detection limit of 0.1 nM. By comparing the different fluorescence responses of CHG NPs and Thioflavin T to Aß aggregation, the Aß oligomerization rate during nucleation can be determined. Moreover, the fluorescence recognition behavior of CHG NPs was selective. CHG NPs specifically bind to negatively charged amyloid aggregates but not to positively charged amyloids and negatively charged soluble proteins. Such enhancement in fluorescence emission is attributed to the clustering-triggered emission effect of CHG NPs after interaction with Aß aggregates via various electronic conjugations and hydrogen bonding, electrostatic, and hydrophobic interactions. Besides fluorescent imaging/probing, CHG NPs over 360 µg/mL could almost completely inhibit the formation of Aß fibrils, exhibiting the capability of regulating Aß aggregation. In-vivo assays with Caenorhabditis elegans CL2006 demonstrated the potency of CHG NPs as an effective theranostic nanoagent for imaging Aß plaques and inhibiting Aß deposition. The findings proved the potential of CHG NPs for development as a potent agent for the diagnosis and treatment of AD.

Nitrogen-Doped Carbonized Polymer Dots: A Potent Scavenger and Detector Targeting Alzheimer's ß-Amyloid Plaques.

The fibrillization and deposition of ß-amyloid protein (Aß) are recognized to be the pathological hallmarks of Alzheimer's disease (AD), which signify the need for the effective detection and inhibition of Aß accumulation. Development of multifunctional agents that can inhibit Aß aggregation, rapidly disaggregate fibrils, and image aggregates is one of the effective strategies to treat and diagnose AD. Herein, the multifunctionality of nitrogen-doped carbonized polymer dots (CPDs) targeting Aß aggregation is reported. CPDs inhibit the fibrillization of Aß monomers and rapidly disintegrate Aß fibrils by electrostatic interactions, hydrogen-bonding and hydrophobic interactions with Aß in a time scale of seconds to minutes. Moreover, the interactions make CPDs label Aß fibrils and emit enhanced red fluorescence by the binding, so CPDs can be used for in vivo imaging of the amyloids in transgenic Caenorhabditis elegans CL2006 as an AD model. Importantly, CPDs are demonstrated to scavenge the in vivo amyloid plaques and to promote the lifespan extension of CL2006 strain by alleviating the Aß-triggered toxicity. Taken together, the multifunctional CPDs show an exciting prospect for further investigations in Aß-targeted AD treatment and diagnosis, and this study provides new insight into the development of carbon materials in AD theranostics.