Nanochemistry of gold: from surface engineering to dental healthcare applications.

Advancements in nanochemistry have led to the development of engineered gold nanostructures (GNSs) with remarkable potential for a variety of dental healthcare applications. These innovative nanomaterials offer unique properties and functionalities that can significantly improve dental diagnostics, treatment, and overall oral healthcare applications. This review provides an overview of the latest advancements in the design, synthesis, and application of GNSs for dental healthcare applications. Engineered GNSs have emerged as versatile tools, demonstrating immense potential across different aspects of dentistry, including enhanced imaging and diagnosis, prevention, bioactive coatings, and targeted treatment of oral diseases. Key highlights encompass the precise control over GNSs' size, crystal structure, shape, and surface functionalization, enabling their integration into sensing, imaging diagnostics, drug delivery systems, and regenerative therapies. GNSs, with their exceptional biocompatibility and antimicrobial properties, have demonstrated efficacy in combating dental caries, periodontitis, peri-implantitis, and oral mucosal diseases. Additionally, they show great promise in the development of advanced sensing techniques for early diagnosis, such as nanobiosensor technology, while their role in targeted drug delivery, photothermal therapy, and immunomodulatory approaches has opened new avenues for oral cancer therapy. Challenges including long-term toxicity, biosafety, immune recognition, and personalized treatment are under rigorous investigation. As research at the intersection of nanotechnology and dentistry continues to thrive, this review highlights the transformative potential of engineered GNSs in revolutionizing dental healthcare, offering accurate, personalized, and minimally invasive solutions to address the oral health challenges of the modern era.

In Situ Immobilization of Multi-Enzymes for Enhanced Substrate Channeling of Enzyme Cascade Reactions: A Nanoarchitectonics Approach by Directed Metal-Organic Frameworks.

Rationally tailoring a controlled spatial organization of enzymes in a nanoarchitecture for multi-enzyme cascade reactions can enhance the catalytic efficiency via substrate channeling. However, attaining substrate channeling is a grand challenge, requiring sophisticated techniques. Herein, we report facile polymer-directed metal-organic framework (MOF)-based nanoarchitechtonics for realizing a desirable enzyme architecture with significantly enhanced substrate channeling. The new method involves the use of poly(acrylamide-co-diallyldimethylammonium chloride) (PADD) as a modulator in a one-step process for simultaneous MOF synthesis and co-immobilization of enzymes (GOx and HRP). The resultant enzymes-PADD@MOFs constructs showed a closely packed nanoarchitecture with enhanced substrate channeling. A transient time close to 0 s was observed, owing to a short diffusion path for substrates in a 2D spindle-shaped structure and their direct transfer from one enzyme to another. This enzyme cascade reaction system showed a 3.5-fold increase in catalytic activity in comparison to free enzymes. The findings provide a new insight into using polymer-directed MOF-based enzyme nanoarchitectures to improve catalytic efficiency and selectivity.

Zero-Carbon Emission Chemical Method to Remove Formaldehyde without Catalyst by Highly Porous Polymer Composites at Room Temperature.

Herein, the fabrication of reduced graphene oxide (RGO)-templated polymer composites for chemical removal of gaseous formaldehyde under ambient conditions is presented. The chemical removal of formaldehyde is achieved by a nucleophilic addition reaction between formaldehyde and aminooxy groups on the polymer chain ends to form the oxime bonds with the only byproduct of H2 O. RGO is essential since it not only has an ultralarge surface area but also can act as a perfect template for immobilizing pyrene-terminated and aminooxy-functionalized polymers via strong π-π stacking interactions, while melamine foam provides a three-dimensional skeleton for loading RGO/polymer composites to afford a porous 3D structure for efficient formaldehyde removal. Since the oxime bond can be cleaved into aminooxy group in acidic media, the RGO/polymer composite can be regenerated for repeatable usage, which shows an excellent performance of adsorbing 14 mg of formaldehyde by 100 mg of the polymer at ambient condition.

Effect of Triton X-100 on the Activity and Selectivity of Lipase Immobilized on Chemically Reduced Graphene Oxides.

The effect of support hydrophobicity on lipase activity and substrate selectivity was investigated with and without Triton X-100 (TX-100). Lipases from Thermomyces lanuginosa (TL) and Alcaligenes sp. (QLM) were immobilized on graphene oxide (GO) and a range of chemically reduced graphene oxides (CRGOs) with different levels of surface hydrophobicity. Activity assays using 4-hydroxy-N-propyl-1,8-naphthalimide (NAP) esters of varying chain lengths (NAP-butyrate (NAP-B), NAP-octanoate (NAP-O), and NAP-palmitate (NAP-P)) showed that the activity of immobilized QLM and TL decreased by more than 60% on GO and 80% on CRGO (2 h), with activity decreasing further as surface hydrophobicity of the CRGOs increased. Across the hydrophobicity range of GO/CRGOs, the substrate selectivity of QLM shifted from more readily hydrolyzing NAP-P to NAP-B, while TL retained its substrate selectivity for NAP-O. Lipase TL was also shown to desorb from GO and 2 h CRGO when mixed with NAP-O and NAP-P, whereas QLM did not. Circular dichroism analyses of the lipase α-helix content correlate to the observed activity data, with decreases in the α-helical content (40% in TL and 20% in QLM relative to free lipase) consistent with decreases in activity after immobilization on GO. α-Helical content decreased even further as the surface hydrophobicity of CRGOs increased. Attenuated total reflectance-Fourier transform infrared spectroscopy also showed significant changes to the lipase secondary structure upon immobilization. The addition of TX-100 into the activity assay modified the substrate selectivity of immobilized QLM, improving the activity against NAP-O (90%) and NAP-P (67%) compared to the activity measured without TX-100. It was shown that TX-100 primarily affected the activity of QLM by interacting with the ester substrate and the lipase itself. This study provides an improved understanding of how support hydrophobicity and the presence of TX-100 can affect activity/selectivity of lipases immobilized on hydrophobic supports.

Effects of gold nanoparticles combined with human ß-defensin 3 on the alveolar bone loss of periodontitis in rat.

BACKGROUND: Nanomaterials of biomedicine and tissue engineering have been proposed for the treatment of periodontitis in recent years. This study aimed to investigate the effects of gold nanoparticles (AuNPs) combined with human ß-defensin 3 (hBD3) on the repair of the alveolar bones of experimental periodontitis in rats. METHODS: A model of experimental periodontitis was established by ligation of the maxillary second molars with silk thread in rats, which were treated with or without AuNPs combined with hBD3. Micro-computerized tomography (micro-CT) scanning, enzyme-linked immunosorbent assay, and histological and immunohistochemical staining, including alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF-κB ligand (RANKL), were used to analyze the samples. RESULTS: Micro-CT demonstrated that the alveolar bone resorption was significantly reduced after the treatment with AuNPs combined with hBD3. Levels of TNF-α and IL-6 were decreased markedly compared with the ligation group. H&E and Masson staining showed that AuNPs combined with hBD3 group had less inflammatory cell infiltration, collagen fibrosis and fracture, but higher calcification in the new bone tissue. Moreover, the administration of AuNPs combined with hBD3 increased the expression levels of ALP and OPG (related to bone formation) while decreasing the expression levels of TRAP and RANKL (related to bone resorption) expression. CONCLUSIONS: AuNPs combined with hBD3 had a protective effect on the progression of experimental periodontitis in rats and played a certain role in suppressing osteoclastogenesis and alleviating the inflammatory destruction of periodontitis along with the promotion of bone repair.

Nel-like Molecule Type 1 Combined with Gold Nanoparticles Modulates Macrophage Polarization, Osteoclastogenesis, and Oral Microbiota in Periodontitis.

The disruption of host-microbe homeostasis and uncontrolled inflammatory response have been considered as vital causes for developing periodontitis, subsequently leading to an imbalance between the bone and immune system and the collapse of bone homeostasis. Consequently, strategies to modulate the immune response and bone metabolization have become a promising approach to prevent and treat periodontitis. In this study, we investigated the cooperative effects of Nel-like molecule type 1 (Nell-1) and gold nanoparticles (AuNPs) on macrophage polarization, osteoclast differentiation, and the corresponding functions in an experimental model of periodontitis in rats. Nell-1-combined AuNPs in in vitro studies were found to reduce the production of inflammatory factors (TNF-α, p < 0.0001; IL-6, p = 0.0012), modulate the ratio of M2/M1 macrophages by inducing macrophage polarization into the M2 phenotype, and inhibit cell fusion, maturation, and activity of osteoclasts. Furthermore, the local application of Nell-1-combined AuNPs in in vivo studies resulted in alleviation of damages to the periodontal and bone tissues, modulation of macrophage polarization and the activity of osteoclasts, and alteration of the periodontal microbiota, in which the relative abundance of the probiotic Bifidobacterium increased (p < 0.05). These findings reveal that Nell-1-combined AuNPs could be a promising drug candidate for the prevention and treatment of periodontitis. However, Nell-1-combined AuNPs did not show organ toxicity or impair the integrity of intestinal epithelium but alter the gut microbiota, leading to the dysbiosis of gut microbiota. The adverse impact of changes in gut microbiota needs to be further investigated. Nonetheless, this study provides a novel perspective and direction for the biological safety assessment of biomaterials in oral clinical applications.

Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment.

The regeneration of lost periodontal apparatus in periodontitis treatment remains a clinical challenge due to the limited regenerative capacity of cementum, periodontal ligament and alveolar bone in periodontitis condition. For periodontal tissue regeneration, it is essential to regulate the inflammatory response and the subsequent differentiation of periodontal cells under the condition due to the infectious nature of the disease. In this study, it was noted that 45 nm gold nanoparticles (AuNPs) could exhibit significant anti-inflammatory effect and improve the periodontal inflammatory microenvironment via regulating inflammatory and regenerative cytokine production and modulating macrophage polarization, subsequently affect the differentiation of human periodontal ligament cells (hPDLCs). With the addition of direct effects of AuNPs on hPDLCs, the periodontal tissue differentiation capacity of hPDLCs in LPS-activated inflammatory macrophage-hPDLCs coculture system was significantly enhanced by the interaction between AuNPs-conditioned macrophage and AuNPs-stimulated hPDLCs. The potential therapeutic application of AuNPs in periodontal tissue regeneration and periodontitis treatment was investigated using both rat fenestration and ligature-induced periodontitis models. It was found that the treatment of 45 AuNPs showed significantly increased newly-formed periodontal attachment, bone and cementum in periodontal defect and less tissue destruction in the progression of periodontitis. This study demonstrated that 45 nm AuNPs could not only directly modulate hPDLCs, but also regulate the early inflammatory response of periodontal tissues via the regulation of macrophage phenotypes, therefore, generate a microenvironment with constraint inflammatory cytokine levels and reparative cytokines such as bone morphogenetic protein-2 (BMP-2), leading to PDLC differentiation, periodontal tissue regeneration and the prevention of periodontitis progression.

Novel sphene coatings on Ti-6Al-4V for orthopedic implants using sol-gel method.

Hydroxyapatite (HAp) is commonly used to coat titanium alloys (Ti-6Al-4V) for orthopedic implants. However, their poor adhesion strength and insufficient long-term stability limit their application. Novel sphene (CaTiSiO5) ceramics possess excellent chemical stability and cytocompatibility. The aim of this study is to use the novel sphene ceramics as coatings for Ti-6Al-4V. The sol-gel method was used to produce the coatings and the thermal properties, phase composition, microstructure, thickness, surface roughness and adhesion strength of sphene coatings were analyzed by differential thermal analysis-thermal gravity (DTA-TG), X-ray diffraction (XRD), scanning electron microscopy (SEM), atom force microscopy (AFM) and scratch test, respectively. DTA analysis confirmed that the temperature of the sphene phase formation is 875 degrees C and XRD analysis indicated pure sphene coatings were obtained. A uniform structure of the sphene coating was found across the Ti-6Al-4V surface, with a thickness and surface roughness of the coating of about 0.5-1 microm and 0.38 microm, respectively. Sphene-coated Ti-6Al-4V possessed a significantly improved adhesion strength compared to that for HAp coating and their chemical stability was evaluated by testing the profile element distribution and the dissolution kinetics of calcium (Ca) ions after soaking the sphene-coated Ti-6Al-4V in Tris-HCl solution. Sphene coatings had a significantly improved chemical stability compared to the HAp coatings. A layer of apatite formed on the sphene-coated Ti-6Al-4V after they were soaked in simulated body fluids (SBF). Our results indicate that sol-gel coating of novel sphene onto Ti-6Al-4V possessed improved adhesion strength and chemical stability, compared to HAp-coated Ti-6Al-4V prepared under the same conditions, suggesting their potential application as coatings for orthopedic implants.

Design of Enzyme Micelles with Controllable Concavo-Convex Micromorphologies for Highly Enhanced Stability and Catalytical Activity.

Concavo-convex micelles with controllable sizes and nanostructures are prepared via self-assembling polymer-enzyme (e.g., shellac enzyme) conjugates with heterogeneous polymer chains, which exhibit higher enzyme stability (300%) and bioactivity (760%) comparing with the well-defined ones. The applied amphiphilic and negatively charged copolymer, poly (methyl methacrylate)-block-poly (sodium p-styrene sulfonate), is synthesized via reversible addition-fragmentation chain transfer polymerization to modify shellac enzyme and immobilize the enzyme bioactivity inducer by covalent conjugation and electrostatic attraction, respectively. The degradation test of catechol confirms the application potential of as-prepared micelles as an efficient and economical decontaminant.

Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery.

Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei. Treatment of tumour-bearing xenograft mice with Apt-DOX resulted in at least 3-fold more inhibition of tumour growth and longer survival as well as a 30-fold lower frequency of CSC and a prolonged longer tumourigenic latency compared with those receiving the same dose of free DOX. Our data demonstrate that a CSC-targeting aptamer is able to transform a conventional chemotherapeutic agent into a CSC-killer to overcome drug resistance in solid tumours.

Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases.

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.