Nanoconfined Silver Nanoclusters Combined with X-Shaped DNA Recognizer-Triggered Cascade Amplification for Electrochemiluminescence Detection of APE1.

Apurinic/apyrimidinic endonuclease 1 (APE1), as a vital base excision repair enzyme, is essential for maintaining genomic integrity and stability, and its abnormal expression is closely associated with malignant tumors. Herein, we constructed an electrochemiluminescence (ECL) biosensor for detecting APE1 activity by combining nanoconfined ECL silver nanoclusters (Ag NCs) with X-shaped DNA recognizer-triggered cascade amplification. Specifically, the Ag NCs were prepared and confined in the glutaraldehyde-cross-linked chitosan hydrogel network using the one-pot method, resulting in a strong ECL response and exceptional stability in comparison with discrete Ag NCs. Furthermore, the self-assembled X-shaped DNA recognizers were designed for APE1 detection, which not only improved reaction kinetics due to the ordered arrangement of recognition sites but also achieved high sensitivity by utilizing the recognizer-triggered cascade amplification of strand displacement amplification (SDA) and DNAzyme catalysis. As expected, this biosensor achieved sensitive ECL detection of APE1 in the range of 1.0 × 10-3 U·µL-1 to 1.0 × 10-10 U·µL-1 with the detection limit of 2.21 × 10-11 U·µL-1, rendering it a desirable approach for biomarker detection.

Nanozyme-Inhibited SERS Multichannel Paper-Based Sensor Array for the Quantification and Identification of Biothiols and Cancer Cells Based on Three Ag-Based Nanomaterials.

Biothiols play essential roles in maintaining normal physiological functions, resisting oxidative stress, and protecting cell health. Establishing an effective and reliable sensor array for the accurate quantification and discrimination of diverse biothiols is extremely meaningful. In this work, Ag/Mn3O4, Ag3PO4, and Ag3Cit with excellent oxidase-mimetic activity and surface-enhanced Raman scattering (SERS)-enhanced features have been prepared and loaded onto Whatman filter paper (WFP) to build SERS paper chips as three sensing channels, which can induce 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to SERS-active reporters (TMBox) and concurrently generate prominent SERS signals. Nevertheless, the addition of biothiols can suppress conversion from TMB to TMBox, which can cause the reduction of the SERS signal from TMBox. Interestingly, each SERS sensing channel can generate different TMBox signals' variations due to differences in the oxidative inhibition abilities of diverse biothiols and exclusive properties of each paper chip, which can be plotted as specific fingerprint patterns of each biothiol and further translated into intuitive two-dimensional (2D) clustering profiles through linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) techniques for precise identification of these six biothiols with the minimum concentration of 1 µM. More importantly, this SERS sensor array is exploited for the precise quantification of intracellular glutathione (GSH), and can differentiate between normal and cancer cells based on different intracellular GSH contents and even identify different types of tumor cells, demonstrating its powerful application prospects in disease diagnosis.

Antibacterial Property and Mechanisms of Au@Ag Core-Shell Nanoparticles with Near-Infrared Absorption Against E. faecalis Infection of Dentin.

Background: Enterococcus faecalis (E. faecalis) is one of the main pathogens responsible for refractory root canal infections in the teeth and shows resistance against various antibacterial managements. Effective control of E. faecalis infection is a prerequisite for successful treatment of refractory apical periodontitis. This study aimed to analyze the antibacterial activity and mechanisms of Au@Ag nanoparticles (NPs) combined with photothermal therapy (PTT) against the original and Ag+-resistant E. faecalis. Methods: Au@AgNPs with optimal shell thicknesses were synthesized and characterized. The antibacterial activity of Au@AgNPs with PTT against the original or Ag+-resistant E. faecalis was evaluated, and the antibiofilm activity was tested on E. faecalis biofilm on the dentin of teeth. The potential antibacterial mechanisms of Au@AgNPs combined with PTT against E. faecalis have also been studied. Moreover, its influence on dentin microhardness and cytotoxicity was assessed. Results: This study revealed that Au@AgNPs combined with PTT showed enhanced antibacterial and antibiofilm effects, no negative effects on dentin microhardness, and low cytotoxicity toward human periodontal ligament cells (hPDLCs). Moreover, Au@AgNPs combined with PTT effectively inhibited the growth of Ag+-resistant E. faecalis. Its antibacterial effects may be exerted through the release of silver ions (Ag+), destruction of the cell membrane, production of reactive oxygen species (ROS) and inhibition of adenosine triphosphate (ATP) production. Hyperthermia generated by Au@AgNPs with PTT reduced membrane fluidity and enhanced Ag+ sensitivity by downregulating fabF expression. The upregulated expression of heat shock genes demonstrated that the Ag+ released from Au@AgNPs compromised the heat adaptation of E. faecalis. Conclusion: PTT significantly enhanced Ag+ sensitivity of the original and Ag+-resistant E. faecalis. Au@AgNPs combined with PTT may have the potential to be developed as a new antibacterial agent to control E. faecalis infections in teeth.

Vanillic Acid Nanocomposite: Synthesis, Characterization Analysis, Antimicrobial, and Anticancer Potentials.

Recently, nanoparticles have received considerable attention owing to their efficiency in overcoming the limitations of traditional chemotherapeutic drugs. In our study, we synthesized a vanillic acid nanocomposite using both chitosan and silver nanoparticles, tested its efficacy against lung cancer cells, and analyzed its antimicrobial effects. We used several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to determine the stability, morphological characteristics, and properties of the biosynthesized vanillic acid nanocomposites. Furthermore, the vanillic acid nanocomposites were tested for their antimicrobial effects against Escherichia coli and Staphylococcus aureus, and Candida albicans. The data showed that the nanocomposite effectively inhibited microbes, but its efficacy was less than that of the individual silver and chitosan nanoparticles. Moreover, the vanillic acid nanocomposite exhibited anticancer effects by increasing the expression of pro-apoptotic proteins (BAX, Casp3, Casp7, cyt C, and p53) and decreasing the gene expression of Bcl-2. Overall, vanillic acid nanocomposites possess promising potential against microbes, exhibit anticancer effects, and can be effectively used for treating diseases such as cancers and infectious diseases.

Mechanistic Investigation on the Antibacterial Activity of Biogenic Silver Nanoparticles Prepared Using Root Extract of Sarsaparilla and Demonstrated their In Vivo Efficacy in Zebrafish Model.

Antibiotic success rates are decreasing as drug-resistant bacteria become more prevalent, prompting the development of new therapeutic drugs. Herein, we demonstrated the antimicrobial activity of sarsaparilla root extract fabricated silver nanoparticles (sAgNPs). The UV-Visible spectra revealed that the surface Plasmon resonance maxima of sAgNPs were at 415 nm. Transmission electron microscopy confirms that the particles are spherical with size of 12-35 nm. The minimum inhibitory concentration (MIC) of sAgNPs against Escherichia coli, uropathogenic Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was 62.5, 62.5, 62.5, 62.5, 125 and 125 µM, respectively. At 1X MIC, sAgNPs induces excess reactive oxygen species (ROS) production and disturbs the bacteria membrane intergity, causing cytoplamic membrane depolarization. Interestingly, antibacterial activity of sAgNPs was considerably reduced in the presence of an antioxidant, N-acetyl cysteine, suggesting that ROS-induced membrane damage is a plausible cause of cell death. In contrast to many studies that only report the in vitro activity of NPs, we determined the in vivo antibacterial efficacy using the zebrafish model. It was found that sAgNPs protect fish from infection by inhibiting bacterial growth and eliminating them from the fish. In addition, the catalytic potential of sAgNPs for wastewater decontamination was demonstrated by degrading organic pollutants such as methyl orange, congo red, reactive black, and acid blue. The pollutants degraded in less than 10 min, and the reaction follows pseudo-first-order kinetics. As a proof of concept, the catalytic potential of sAgNPs in degrading mixed dyes to satisfy industrial wastewater treatment needs was established. In summary, sAgNPs have the potential to act as nanocatalysts and nano-drugs, addressing key challenges in medical and environmental research.

Natural dyes developed by microbial-nanosilver to produce antimicrobial and anticancer textiles.

Developing special textiles (for patients in hospitals for example) properties, special antimicrobial and anticancer, was the main objective of the current work. The developed textiles were produced after dyeing by the novel formula of natural (non-environmental toxic) pigments (melanin amended by microbial-AgNPs). Streptomyces torulosus isolate OSh10 with accession number KX753680.1 was selected as a superior producer for brown natural pigment. By optimization processes, some different pigment colors were observed after growing the tested strain on the 3 media. Dextrose and malt extract enhanced the bacteria to produce a reddish-black color. However, glycerol as the main carbon source and NaNO3 and asparagine as a nitrogen source were noted as the best for the production of brown pigment. In another case, starch as a polysaccharide was the best carbon for the production of deep green pigment. Peptone and NaNO3 are the best nitrogen sources for the production of deep green pigment. Microbial-AgNPs were produced by Fusarium oxysporum with a size of 7-21 nm, and the shape was spherical. These nanoparticles were used to produce pigments-nanocomposite to improve their promising properties. The antimicrobial of nanoparticles and textiles dyeing by nanocomposites was recorded against multidrug-resistant pathogens. The new nanocomposite improved pigments' dyeing action and textile properties. The produced textiles had anticancer activity against skin cancer cells with non-cytotoxicity detectable action against normal skin cells. The obtained results indicate to application of these textiles in hospital patients' clothes.

Heteroatom Doping Promoted Ultrabright and Ultrastable Photoluminescence of Water-Soluble Au/Ag Nanoclusters for Visual and Efficient Drug Delivery to Cancer Cells.

Photoluminescence (PL) metal nanoclusters (NCs) have attracted extensive attention due to their excellent physicochemical properties, good biocompatibility, and broad application prospects. However, developing water-soluble PL metal NCs with a high quantum yield (QY) and high stability for visual drug delivery remains a great challenge. Herein, we have synthesized ultrabright l-Arg-ATT-Au/Ag NCs (Au/Ag NCs) with a PL QY as high as 73% and excellent photostability by heteroatom doping and surface rigidization in aqueous solution. The as-prepared Au/Ag NCs can maintain a high QY of over 61% in a wide pH range and various ionic environments as well as a respectable resistance to photobleaching. The results from structure characterization and steady-state and time-resolved spectroscopic analysis reveal that Ag doping into Au NCs not only effectively modifies the electronic structure and photostability but also significantly regulates the interfacial dynamics of the excited states and enhances the PL QY of Au/Ag NCs. Studies in vitro indicate Au/Ag NCs have a high loading capacity and pH-triggered release ability of doxorubicin (DOX) that can be visualized from the quenching and recovery of PL intensity and lifetime. Imaging-guided experiments in cancer cells show that DOX of Au/Ag NCs-DOX agents can be efficiently delivered and released in the nucleus with preferential accumulation in the nucleolus, facilitating deep insight into the drug action sites and pharmacological mechanisms. Moreover, the evaluation of anticancer activity in vivo reveals an outstanding suppression rate of 90.2% for mice tumors. These findings demonstrate Au/Ag NCs to be a superior platform for bioimaging and visual drug delivery in biomedical applications.

Anti-tumor therapy through high ROS performance induced by Ag nanoenzyme from boron cluster with halloysite clay nanotubes.

The conventional silver nanoparticles (Ag NPs) are characterized with high loading rate and stacking phenomenon, leading to shedding caused biotoxicity and low catalytic efficiency. This seriously hinders their application in biomedicine. Here, we modified the highly dispersible Ag NPs and Ag single-atoms (SAs) synthesis by combining the halloysite clay nanotubes (HNTs) and dodecahydro-dodecaborate (closo-[B12H12]2-) to increase the biocompatible properties and decrease the loading rate. This novel Ag single-atom nanoenzyme alongside Ag NPs nanoenzyme avoid the elevated-temperature calcination while maintaining the exceptionally high-level efficiency of Ag utilization via the reducibility and coordination stabilization of closo-[B12H12]2- and HNTs. With theoretical calculation and electron paramagnetic resonance, we confirmed that both Ag SAzymes and Ag NPs in HNT@B12H12@Ag nanoenzyme are capable decompose the H2O2 into hydroxyl radical (·OH). For the application, we investigated the catalytic activity in the tumor cells and antitumor effects of HNT@B12H12@Ag nanoenzyme both in vitro and in vivo, and confirmed that it effectively suppressed melanoma growth through ·OH generation, with limited biotoxicity. This study provides a novel Ag nanoenzyme synthesis approach to increase the possibility of its clinical application.

Enhanced anticancer activity of silver doped zinc oxide magnetic nanocarrier loaded with sorafenib for hepatocellular carcinoma treatment.

Drug delivery is the process or method of delivering a pharmacological product to have therapeutic effects on humans or animals. The use of nanoparticles to deliver medications to cells is driving the present surge in interest in improving human health. Green nanodrug delivery methods are based on chemical processes that are acceptable for the environment or that use natural biomaterials such as plant extracts and microorganisms. In this study, zinc oxide-superparamagnetic iron oxide-silver nanocomposite was synthesized via green synthesis method using Fusarium oxysporum fungi mycelia then loaded with sorafenib drug. The synthesized nanocomposites were characterized by UV-visibile spectroscopy, FTIR, TEM and SEM techniques. Sorafenib is a cancer treatment and is also known by its brand name, Nexavar. Sorafenib is the only systemic medication available in the world to treat hepatocellular carcinoma. Sorafenib, like many other chemotherapeutics, has side effects that restrict its effectiveness, including toxicity, nausea, mucositis, hypertension, alopecia, and hand-foot skin reaction. In our study, 40 male albino rats were given a single dose of diethyl nitrosamine (DEN) 60 mg/kg b.wt., followed by carbon tetrachloride 2 ml/kg b.wt. twice a week for one month. The aim of our study is using the zinc oxide-superparamagnetic iron oxide-silver nanocomposite that was synthesized by Fusarium oxysporum fungi mycelia as nanocarrier for enhancement the sorafenib anticancer effect.

Gemcitabine and synthesized silver nanoparticles impact on chemically induced hepatocellular carcinoma in male rats.

Objective: Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficiency of co-treating gemcitabine and silver nanoparticles in treating hepatocellular carcinoma. Method: The AgNPs were characterized using UV-visible spectroscopy, XRD, TEM, and EDX. The MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. After HCC development, rats received (10 µg/g b.wt.) of AgNPs three times a week for 4 weeks and/or GEM (5 mg/kg b.wt.) twice weekly for 4 weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. Results: The co-treatment of GEM and AgNPs increased apoptosis by upregulating Bax and caspase 9 while diminishing Bcl2 and SMAD4. It also improved cytochrome P450 m-RNA relative expression. The results also proved the cooperation between GEM and AgNPs in deactivating miR21. The impact of AgNPs as an adjuvant treatment with GEM was recognized. Conclusions: The study showed that co-treating AgNPs and GEM can improve the efficiency of GEM alone in treating HCC. This is achieved by enhancing intrinsic and extrinsic apoptotic pathways while diminishing some drawbacks of using GEM alone.

Synergy of Target-Induced Magnetic Network and Single-Drop Chromogenic System for Ultrasensitive "All-in-Tube" Detection of miRNA in Whole Blood.

The development of liquid biopsy methods for the accurate and reliable detection of miRNAs in whole blood is critical for the early diagnosis and monitoring of diseases. However, accurate quantification of miRNA expression levels remains challenging due to the complex matrix and low abundance of miRNAs in blood samples. Herein, we report a contactless signal output strategy with low background interference that ensures "zero-contact" between the reaction system and the colorimetry system. The designed target-induced magnetic ZnS/ZIF-90/ZnS network can serve as a unique signal amplifier and transducer. It releases hydrogen sulfide (H2S) gas in an acidic solution which can be concentrated in a droplet of only a few microliters in volume, etching the silver layer of Au@Ag nanostars (NSTs) in the droplet. This will lead to changes in the localized surface plasmon resonance signals of the NSTs. Finally, quantitative detection of let-7a is realized by measuring the offset value of the UV-vis absorption peak. Therefore, by virtue of the synergistic action of quadruple signal amplification methods, including catalytic hairpin assembly, ZnS/ZIF-90/ZnS, magnetic separation, and microextraction, the "All-in-Tube" ultrasensitive detection of low-abundance let-7a in whole blood is achieved with a detection limit as low as the aM level. In addition, the "zero-contact" signal output mode effectively solves the problem of complex matrix interference, demonstrating the great potential of this method for miRNA quantification in complex samples, such as whole blood.

Implications of silver nanoparticles for H. pylori infection: modulation of CagA function and signaling.

Background: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. Methods: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. Results: AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. Conclusion: Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.

Anticancer efficacy of biosynthesized silver nanoparticles loaded with recombinant truncated parasporin-2 protein.

Bacterial toxins have received a great deal of attention in the development of cancer treatments. Parasporin-2 (PS2Aa1 or Mpp46Aa1) is a Bacillus thuringiensis parasporal protein that preferentially destroys human cancer cells while not harming normal cells, making it a promising anticancer treatment. With the efficient development and sustainable silver nanoparticles (AgNPs) synthesis technology, the biomedical use of AgNPs has expanded. This study presents the development of a novel nanotoxin composed of biosynthesized silver nanoparticles loaded with the N-terminal truncated PS2Aa1 toxin. MOEAgNPs were synthesized using a biological method, with Moringa oleifera leaf extract and maltose serving as reducing and capping agents. The phytochemicals present in M. oleifera leaf extract were identified by GC-MS analysis. MOEAgNPs were loaded with N-terminal truncated PS2Aa1 fused with maltose-binding protein (MBP-tPS2) to formulate PS2-MOEAgNPs. The PS2-MOEAgNPs were evaluated for size, stability, toxin loading efficacy, and cytotoxicity. PS2-MOEAgNPs demonstrated dose-dependent cytotoxicity against the T-cell leukemia MOLT-4 and Jurkat cell lines but had little effect on the Hs68 fibroblast or normal cell line. Altogether, the current study provides robust evidence that PS2-MOEAgNPs can efficiently inhibit the proliferation of T-cell leukemia cells, thereby suggesting their potential as an alternative to traditional anticancer treatments.

Infection microenvironment-triggered nanoparticles eradicate MRSA by thermally amplified chemodynamic therapy and M1 macrophage.

It is of great significance to develop a novel approach to treat bacterial infections, as the frequent misuse of antibiotics leads to the serious problem of bacterial resistance. This study proposed antibiotic-free antibacterial nanoparticles for eliminating methicillin-resistant Staphylococcus aureus (MRSA) based on a multi-model synergistic antibacterial ability of chemodynamic therapy (CDT), photothermal effect, and innate immunomodulation. Specifically, a polydopamine (PDA) layer coated and Ag nanoparticles loaded core-shell structure Fe3O4 nanoparticles (Fe3O4@PDA-Ag) is prepared. The Fe3O4 catalyzes H2O2 present in acidic microenvironment of bacterial infection into more toxic reactive oxygen species (ROS) and synergizes with the released Ag ions to exert a stronger bactericidal capacity, which can be augmented by photothermal action of PDA triggered by near-infrared light and loosen the biofilm by photothermal action to promote the penetration of ROS and Ag ion into the biofilm, result in disrupting biofilm structure along with killing encapsulated bacteria. Furthermore, Fe3O4@PDA-Ag exerts indirect antibacterial effects by promoting M1 macrophage polarizing. Animal models demonstrated that Fe3O4@PDA-Ag effectively controlled MRSA-induced infections through photothermal enhanced CDT, Ag+ releasing, and macrophage-mediated bactericidal properties. The acid-triggered antibacterial nanoparticles are expected to combat drug-resistant bacteria infection.

Eco-friendly Nanoparticles Synthesized from Salvia sclarea Ethanol Extract Protect against STZ-induced Diabetic Nephropathy in Rats via Antioxidant, Anti-inflammatory, and Apoptosis Mechanisms.

Recent global scientific attention has been directed towards eco-friendly synthesis and versatile applications of silver nanoparticles (AgNPs) due to their effectiveness against specific cells and tissues. This study aimed to develop a green synthesis method for AgNPs using ethanolic extract from Salvia sclarea aerial parts, and to assess their protective efficacy against streptozotocin (STZ)-induced diabetic nephropathy in rats. Additionally, antioxidant, anti-inflammatory, and apoptosis studies were conducted to understand their mode of action. Characterization via ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and X-ray diffraction (XRD) confirmed the formation of ethanol extract of Salvia sclarea silver nanoparticles (EESS AgNPs), with a distinctive absorption peak at 400 nm. Scanning electron microscopy (SEM) analysis revealed predominantly spherical and quasi-spherical shapes of the synthesized nanoparticles. The treatment procedure spanned for a period of 12 weeks in diabetic rats and were evaluated for inflammatory markers (tumor necrosis factor-α, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) and apoptosis markers (Bcl-2, Bax, cleaved-caspase-3). Results demonstrated that treatment with EESS AgNPs significantly reduced blood glucose levels compared to the diabetic group. Additionally, EESS AgNPs treatment led to a significant decrease in levels of pro-inflammatory cytokines TNF-α, IL-1ß, and PKC-ꞵ in renal cells. Furthermore, EESS AgNPs effectively modulated antioxidant enzyme concentrations, including GSH, SOD, GPx, and CAT, bringing them to acceptable levels. Administration of EESS AgNPs also resulted in a significant decrease in protein levels of Bax and activated caspase-3, while increasing expression of the anti-apoptotic protein Bcl-2 in renal cells of STZ-induced diabetic rats. In conclusion, EESS AgNPs demonstrate potent anti-hyperglycemic effects, potentially mitigating diabetic nephropathy by suppressing hyperglycemiainduced oxidative stress, apoptosis, and inflammation in renal cells of diabetic rats.

Study on the Antibacterial Activity and Bone Inductivity of Nanosilver/PLGA-Coated TI-CU Implants.

Background: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. Purpose: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. Methods: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Results: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. Conclusion: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.

SERS biosensors based on catalytic hairpin self-assembly and hybridization chain reaction cascade signal amplification strategies for ultrasensitive microRNA-21 detection.

A highly sensitive surface-enhanced Raman scattering (SERS) biosensor has been developed for the detection of microRNA-21 (miR-21) using an isothermal enzyme-free cascade amplification method involving catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). The CHA reaction is triggered by the target miR-21, which causes hairpin DNA (C1 and C2) to self-assemble into CHA products. After AgNPs@Capture captures the resulting CHA product, the HCR reaction is started, forming long-stranded DNA on the surface of AgNPs. A strong SERS signal is generated due to the presence of a large amount of the Raman reporter methylene blue (MB) in the vicinity of the SERS "hot spot" on the surface of AgNPs. The monitoring of the SERS signal changes of MB allows for the highly sensitive and specific detection of miR-21. In optimal conditions, the biosensor exhibits a satisfactory linear range and a low detection limit for miR-21 of 42.3 fM. Additionally, this SERS biosensor shows outstanding selectivity and reproducibility. The application of this methodology to clinical blood samples allows for the differentiation of cancer patients from healthy controls. As a result, the CHA-HCR amplification strategy used in this SERS biosensor could be a useful tool for miRNA detection and early cancer screening.

Extracellular Matrix Mimicking Wound Microenvironment Responsive Amyloid-Heparin@TAAgNP Co-Assembled Hydrogel: An Effective Conductive Antibacterial Wound Healing Material.

Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.

Enhancing CRISPR/Cas-mediated electrochemical detection of nucleic acid using nanoparticle-labeled covalent organic frameworks reporters.

Molecular detection of nucleic acid plays an important role in early diagnosis and therapy of disease. Herein, a novel and enhanced electrochemical biosensor was exploited based on target-activated CRISPR/Cas12a system coupling with nanoparticle-labeled covalent organic frameworks (COFs) as signal reporters. Hollow spherical COFs (HCOFs) not only served as the nanocarriers of silver nanoparticles (AgNPs)-DNA conjugates for enhanced signal output but also acted as three-dimensional tracks of CRISPR/Cas12a system to improve the cleavage accessibility and efficiency. The presence of target DNA triggered the trans-cleavage activity of the CRISPR/Cas12a system, which rapidly cleaved the AgNPs-DNA conjugates on HCOFs, resulting in a remarkable decrease of the electrochemical signal. As a proof of concept, the fabricated biosensing platform realized highly sensitive and selective detection of human papillomavirus type 16 (HPV-16) DNA ranging from 100 fM to 1 nM with the detection limit of 57.2 fM. Furthermore, the proposed strategy provided a versatile and high-performance biosensor for the detection of different targets by simple modification of the crRNA protospacer, holding promising applications in disease diagnosis.

Application of green synthesized silver nanoparticles in Burn therapy: a review.

Silver nanoparticles (AgNPs), owing to their unusual characteristics, have been used in various pharmaceutical, cosmetic, and healthcare products. AgNPs, with their exceptional biological potential, exhibit antibacterial, antifungal, antiviral, anti-inflammatory, anticancer, and wound healing properties and have been extensively used in burn therapy. Several studies have established the use of silver nanoparticles in the treatment of burn injuries, resulting in reduced inflammation, quick tissue regeneration, and the remarkable creation of collagen fibers. Conventional physical and chemical techniques have synthesized AgNPs, but they appear to be highly costly and hazardous. Recently, there has been considerable interest in the synthesis of AgNPs using the green chemistry approach because of its tremendous benefits, including being non-toxic, low energy consumption, pollution-free, economical, environmentally friendly, and more sustainable. This review emphasizes the green synthesis of AgNPs using bacteria, fungi, plants, and other microorganisms and the current research related to the application of green synthesized AgNPs in burn therapy, including the biological aspects of AgNPs, their mode of action, and any possible detrimental effects.