A Pt1Pd Single-Atom Alloy Nanozyme with Boosted Enzyme-Like Activity for Efficient Photo-Mediated Tumor Therapy.

Single-atom nanozymes (SAzymes) are emerging natural enzyme mimics and have attracted much attention in the biomedical field. SAzymes with Metal─Nx sites designed on carbon matrixes are currently the mainstream in research. It is of great significance to further expand the types of SAzymes to enrich the nanozyme library. Single-atom alloys (SAAs) are a material in which single-atom metal sites are dispersed onto another active metal matrix, and currently, there is limited research on their enzyme-like catalytic performance. In this work, a biodegradable Pt1Pd SAA is fabricated via a simple galvanic replacement strategy, and for the first time reveals its intrinsic enzyme-like catalytic performance including catalase-, oxidase-, and peroxidase-like activities, as well as its photodynamic effect. Experimental characterizations demonstrate that the introduction of single-atom Pt sites contributes to enhancing the affinity of Pt1Pd single-atom alloy nanozyme (SAAzyme) toward substrates, thus exhibiting boosted catalytic efficiency. In vitro and in vivo experiments demonstrate that Pt1Pd SAAzyme exhibits a photo-controlled therapeutic effect, with a tumor inhibition rate of up to 100%. This work provides vital guidance for opening the research direction of SAAs in enzyme-like catalysis.

The Effect of Chitosan in Wound Healing: A Systematic Review.

OBJECTIVE: To systematically review the effectiveness of chitosan in wound healing. DATA SOURCES: References were retrieved from PubMed, EMBASE, the Cochrane library, and Web of Science based on Medical Subject Headings and keywords ("chitosan" OR "chitin" OR "poliglusam" AND "wound healing"). STUDY SELECTION: Eligible articles were randomized controlled trials (RCTs) that required interventions for chitosan and its derivative dressings and included endpoints associated with wound healing. In summary, five RCTs (N = 319) were included in the final analysis. DATA SYNTHESIS: Only two RCTS (40%) reported significant beneficial effects of chitosan on wound healing compared with conventional gauze dressings (eg, tulle gras, petroleum jelly). The remaining three studies reported that chitosan had no significant effect on clinical wound healing compared with other biologic dressings (eg, alginate, hydrocolloid). CONCLUSIONS: Although the number of trials of new chitosan dressings has been increasing, studies on the relationship between chitosan and wound healing have been limited. Current data suggest that chitosan does not slow wound healing. However, the small number of available trials restricted adequate interpretation of the existing results. Future research needs to be rigorously designed to confirm any clinically relevant effect of chitosan in wound healing.

Engineered liposomes targeting hepatic stellate cells overcome pathological barriers and reverse liver fibrosis.

Dual pathological barriers, including capillarized liver sinusoidal endothelial cells (LSECs) and deposited extracellular matrix (ECM), result in insufficient drug delivery, significantly compromising the anti-fibrosis efficacy. Additionally, excessive reactive oxygen species (ROS) in the hepatic microenvironment are crucial factors contributing to the progression of liver fibrosis. Hence, hyaluronic acid (HA) modified liposomes co-delivering all-trans retinoic acid (RA) and L-arginine (L-arg) were constructed to reverse hepatic fibrosis. By exhibiting exceptional responsiveness to the fibrotic microenvironment, our cleverly constructed liposomes efficiently disrupted the hepatic sinus pathological barrier, leading to enhanced accumulation of liposomes in activated hepatic stellate cells (HSCs) and subsequent induction of HSCs quiescence. Specially, excessive ROS in liver fibrosis promotes the conversion of loaded L-arg to nitric oxide (NO). The ensuing NO serves to reestablish the fenestrae structure of capillarized LSECs, thereby augmenting the likelihood of liposomes reaching the hepatic sinus space. Furthermore, subsequent oxidation of NO by ROS into peroxynitrite activates pro-matrix metalloproteinases into matrix metalloproteinases, which further disrupts the deposited ECM barrier. Consequently, this NO-induced cascade process greatly amplifies the accumulation of liposomes within activated HSCs. More importantly, the released RA could induce quiescence of activated HSCs by significantly downregulating the expression of myosin light chain-2, thereby effectively mitigating excessive collagen synthesis and ultimately leading to the reversal of liver fibrosis. Overall, this integrated systemic strategy has taken a significant step forward in advancing the treatment of liver fibrosis.

Precipitation contributes to alleviating pollution of rubber-derived chemicals in receiving watersheds: Combining confluent stormwater runoff from different functional areas.

The release of rubber-derived chemicals (RDCs) in road surface runoff has received significant attention. Urban surface runoff is often the confluence of stormwater runoff from specific areas. However, the impact of precipitation on RDCs contamination in confluent stormwater runoff and receiving watersheds remains poorly understood. Herein, we investigated the profiles of RDCs and their transformation products in confluent stormwater runoff and receiving rivers affected by precipitation events. The results showed that 34 RDCs are ubiquitously present in confluent stormwater runoff and surface water, with mean concentrations of 1.03-2749 and 0.28-436 ng/L, respectively. The most dominant target compounds in each category were N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, 2-benzothiazolol, and 1,3-diphenylguanidine. Total RDCs concentrations in confluent stormwater runoff decreased spatially from industrial areas to business districts to college towns. A significant decrease in RDCs levels in surface water after rainfall was observed (P < 0.01), indicating that precipitation contributes to alleviating RDCs pollution in receiving watersheds. To our knowledge, this is the first report of N,N'-ditolyl-p-phenylenediamine quinone (DTPD-Q) levels in surface waters in China. The annual mass load of ∑RDCs reached 72,818 kg/y in confluent stormwater runoff, while 38,799 kg/y in surface water. The monitoring of confluent stormwater runoff is an efficient measure for predicting contamination loads from RDCs in rivers. Risk assessment suggested that most RDCs posed at least medium risks to aquatic organisms, especially 6PPD-quinone. The findings help to understand the environmental fate and risks of RDCs in the confluent stormwater runoff and receiving environments after precipitation events.

Pathological environment directed in situ peptidic supramolecular assemblies for nanomedicines.

Peptidic self-assembly provides a powerful method to build biomedical materials with integrated functions. In particular, pathological environment instructed peptidic supramolecular have gained great progress in treating various diseases. Typically, certain pathology related factors convert hydrophilic precursors to corresponding more hydrophobic motifs to assemble into supramolecular structures. Herein, we would like to review the recent progress of nanomedicines based on the development of instructed self-assembly against several specific disease models. Firstly we introduce the cancer instructed self-assembly. These assemblies have exhibited great inhibition efficacy, as well as enhanced imaging contrast, against cancer models both in vitro and in vivo. Then we discuss the infection instructed peptidic self-assembly. A number of different molecular designs have demonstrated the potential antibacterial application with satisfied efficiency for peptidic supramolecular assemblies. Further, we discuss the application of instructed peptidic self-assembly for other diseases including neurodegenerative disease and vaccine. The assemblies have succeeded in down-regulating abnormal Aß aggregates and immunotherapy. In summary, the self-assembly precursors are typical two-component molecules with (1) a self-assembling motif and (2) a cleavable trigger responsive to the pathological environment. Upon cleavage, the self-assembly occurs selectively in pathological loci whose targeting capability is independent from active targeting. Bearing the novel targeting regime, we envision that the pathological conditions instructed peptidic self-assembly will lead a paradigm shift on biomedical materials.

One-pot, self-catalyzed synthesis of self-adherent hydrogels for photo-thermal, antimicrobial wound treatment.

Self-adhering hydrogels are promising materials to be employed as wound dressings, because they can be used for wound healing without the necessity of additional stitching. However, micro-organisms can easily adhere to these hydrogels as well, which usually causes wound infections. Therefore, adhesive hydrogels are often combined with antibiotics. However, this introduces a risk of drug resistance, cytotoxicity and poor cell affinity. Consequently, recently, there has been great interest in developing non-antibiotic, antibacterial adhesive hydrogels. In this article, we present a simple one-pot synthesis procedure to prepare self-adhesive hydrogels composed of poly(acrylamide) (PAM), naturally derived chitosan (CS) and tannic acid/ferric ion chelates (TA@Fe3+). TA@Fe3+ enables self-catalysis of the polymerization reaction. In addition, due to its near infrared (NIR) photothermal responsiveness, TA@Fe3+ allows for eliminating the bacterial activity with up to 91.6% and 94.7% effectivity against Escherichia coli and Staphylococcus aureus, respectively. Mechanical and adhesion testing shows that the hydrogels are tough as well as flexible and will adhere repeatedly to many types of biological tissues, which can be attributed to the combination of physical and chemical bonding between TA@Fe3+ and PAM and CS, respectively. Moreover, in vitro and in vivo tests indicate that the NIR photothermally active hydrogel can effectively prevent bacterial infection and accelerate tissue regeneration, which demonstrates that these hydrogels are promising functional materials for wound healing applications.

Salivary gland ultrasonography in primary Sjögren's syndrome from diagnosis to clinical stratification: a multicentre study.

BACKGROUND: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren's syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study. METHODS: SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS. RESULTS: The US scores in the pSS group were significantly higher than those in the non-pSS group (p < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the left (right) parotid gland and the left (right) submandibular gland was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. CONCLUSIONS: SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.

Highly Stretchable and Conductive Self-Healing Hydrogels for Temperature and Strain Sensing and Chronic Wound Treatment.

Flexible bioelectronics for biomedical applications requires a stretchable, conductive, self-healable, and biocompatible material that can be obtained by cost-effective chemicals and strategies. Herein, we synthesized polypyrrole or Zn-functionalized chitosan molecules, which are cross-linked with poly(vinyl alcohol) to form a hydrogel through dynamic di-diol complexations, hydrogen bonding, and zinc-based coordination bonds. These multiple dynamic interactions endow the material with excellent stretchability and autonomous self-healing ability. The choice of Food and Drug Administration (FDA)-approved materials (poly(vinyl alcohol) and chitosan) as the matrix materials ensures the good biocompatibility of the hydrogel. The conductivity contributed by the polypyrrole allowed the hydrogel to sense strain and temperature, and the coordinated Zn significantly enhanced the antibacterial activity of the hydrogel. Moreover, using a diabetic rat model, we have proved that this hydrogel is capable of promoting the healing of the infected chronic wounds with electrical stimulation.

Enzyme-Instructed Supramolecular Self-Assembly with Anticancer Activity.

Cancer remains one of the leading causes of death, which has continuously stimulated the development of numerous functional biomaterials with anticancer activities. Herein is reviewed one recent trend of biomaterials focusing on the advances in enzyme-instructed supramolecular self-assembly (EISA) with anticancer activity. EISA relies on enzymatic transformations to convert designed small-molecular precursors into corresponding amphiphilic residues that can form assemblies in living systems. EISA has shown some advantages in controlling cell fate from three aspects. 1) Based on the abnormal activity of specific enzymes, EISA can differentiate cancer cells from normal cells. In contrast to the classical ligand-receptor recognition, the targeting capability of EISA relies on dynamic control of the self-assembly process. 2) The interactions between EISA and cellular components directly disrupt cellular processes or pathways, resulting in cell death phenotypes. 3) EISA spatiotemporally controls the distribution of therapeutic agents, which boosts drug delivery efficiency. Therefore, with regard to the development of EISA, the aim is to provide a perspective on the future directions of research into EISA as anticancer theranostics.

Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates.

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15∼0.3 and 1:3:0.2∼0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.

The Synergetic Effects of Nonpolar and Polar Protic Solvents on the Properties of Felodipine and Soluplus in Solutions, Casting Films, and Spray-Dried Solid Dispersions.

The aim was to explore the effects of nonpolar and polar protic solvents composed of dichloromethane (DCM) and ethanol (EtOH) on the properties of felodipine (FLDP) and Soluplus in solutions, casting films, and spray-dried drug-rich or polymer-rich solid dispersions (SDs). Measurement of intrinsic viscosity and solubility indicated that FLDP and Soluplus were miscible. EtOH-DCM ranging from 20:80 to 50:50 induced the strongest molecular interactions for FLDP-Soluplus-solvents systems. Accordingly, the casting films and spray-dried powders of FLDP and Soluplus were prepared using pure EtOH or DCM and their mixtures as solvents. Polarized light microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro dissolution tests, and stability have been conducted to characterize these films or spray-dried powders. EtOH-DCM (50:50) showed δH 2-3 MPa1/2 higher than FLDP and Soluplus. It exhibited stronger inhibitory effects on phase separation and recrystallization of amorphous FLDP than pure DCM or EtOH in the drug-rich casting films, spray drying process, and spray-dried SDs exposure to 40°C/RH75% for 1 month. Higher ratio of Soluplus may offset the effects of solvents on the dissolution and stability of polymer-rich SDs. In conclusion, combination of nonpolar and polar protic solvents is of high potential for spray drying to optimize drug-rich SDs.

Novel self-assembled tacrolimus nanoparticles cross-linking thermosensitive hydrogels for local rheumatoid arthritis therapy.

The aim was to explore the potential application of novel self-assembled nanoparticles cross-linking thermosensitive hydrogels composed of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and tacrolimus (FK-506) for local therapy of rheumatoid arthritis (RA). The sol-gel transition temperature (Tsol-gel), gelation time, rheological behaviors, in vitro release, in vivo gelation and retention, and therapeutic efficacy against adjuvant-induced arthritis (AIA) rats were compared between the Soluplus hydrogels and widely studied poloxamer 407 (P407) delivery systems. In sol, the spherical and uniform FK506 loaded Soluplus nanoparticles (Soluplus-SNPs) were self-assembled with encapsulation efficiency of 99.5±1.5% and particle size of 73.9±2.9nm. The decreased Tsol-gel of Soluplus-SNPs hydrogels was associated with the addition of salts, elevation of pH and ionic strength. The optimal Tsol-gel of Soluplus-SNPs with concentrations of 10%-30% in phosphate buffer (50mM, pH 7.4) was from 37.4±0.1°C to 32.8±0.3°C and the gelation time was not greater than 2min. Soluplus-SNPs gelling systems showed lower viscosity and wider range concentrations in sol state at 25°C and stronger gel strength at 37°C than P407, which resulting in longer sustained release of FK506 but without burst-release in vitro, and longer retention time in the local injection site in vivo. The therapeutic efficacy to treat AIA rats was significantly enhanced from d10 to d17 after a single dose of FK506 loaded in 10% and 20% Soluplus-SNPs hydrogels. In conclusion, Soluplus-SNPs hydrogel is a potential sustainable delivery system for FK506 to treat RA locally.

Supramolecular Polymer Dot Ensemble for Ratiometric Detection of Lectins and Targeted Delivery of Imaging Agents.

A supramolecular, polymer-dot-based ensemble has been developed for the ratiometric detection of lectins and targeted delivery of glycoprobes. Self-assembly between a blue-emitting polymer dot and a red-emitting glycoprobe, results in an ensemble that shows red emission upon excitation of the polymer dot because of Förster resonance energy transfer. Resulting in ratiometric detection of lectins in buffer solution as well as targeted delivery of the glycoprobe to cells that highly express a sugar receptor. Unlike conventional systems where both the agent and vector are codelivered intracellularly, our ensemble developed here shows a receptor-controlled dissociation on the cell membrane.