Synthesis and antimicrobial activity testing of quaternary ammonium silane compounds.

With increasing health awareness of the pathogenic effects of disease-causing microorganisms, interest in and use (of medical textiles, disinfectants in medical devices, etc.) of antimicrobial substances have increased in various applications, such as medical textiles and disinfectants (alcohol-based and nonalcoholic), in medical devices There are several concerns with alcohol-based disinfectants, such as surface deformation of medical devices due to high alcohol content and damage to skin tissue caused by lipid and protein denaturation of cell membranes. Quaternary ammonium compounds (quats) were preferred because they have the potential to prepare water-based disinfectants. In this study, novel (3-chloropropyl)triethoxysilane (CPTMO) and (3-chloropropyl)triethoxysilane (CPTEO) based quaternary ammonium silane compounds (silane-quats) were developed using quats with carbon chain lengths of C12, C14, C16 and C18. Titration (ASTM D2074) was used to calculate the yield of the synthesis and the structures of the products were characterised by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (13C NMR, 1H NMR) and gas chromatography-mass spectrometry (GC-MS).The in vitro antimicrobial activity of the synthesized samples was evaluated against Gram-positive (Staphylococcus aureus (S. aureus), Enterococcus hirae (E. hirae)) and Gram-negative (Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa)) bacteria and fungi (Candida albicans (C. albicans), Aspergillus brasiliensis (A. brasiliensis)) using the minimum inhibitory concentration (MIC) test. According to MIC tests, the silane-quats with the highest antimicrobial effects were dimethylhexadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (SQ3), which had an MIC of < 16 µg/ml (ppm) against E. coli, S. aureus, E. hirae, C. albicans, and A. brasiliensis and 32 µg/ml against P. aeruginosa. The MIC test results also showed antimicrobial activity at least 2 times greater than that of the commercially available disinfectant benzalkonium chloride (BAC). Findings suggest that SQ3 (C16) holds promise as an effective medical disinfectant, presenting a novel approach to combating microbial infections in healthcare settings.

Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

Superhydrophobic coatings reduce human bacterial foodborne pathogen attachment to woods used in fresh produce harvest and postharvest packing.

Wood is reportedly more difficult to maintain in hygienic condition versus other food contact materials, yet its use in produce packing and retail warrants efforts to reduce the risk of microbial pathogen contamination and attachment. This study characterized antifouling capabilities of fluorinated silanes applied to wood used in fresh edible produce handling to render the wood superhydrophobic and less supportive of bacterial pathogen attachment. Pine and oak cubic coupon surfaces were treated with 1% (w/w) silane or left untreated. Treated and untreated coupons were inoculated with Salmonella enterica or Listeria monocytogenes and held to facilitate pathogen attachment for 1, 4, or 8 h. Silane treatment of wood produced significant reductions in the proportions of strongly attaching cells for both pathogens versus loosely attaching cells (P < 0.01). Salmonella attachment demonstrated a dependency on wood treatment; silane-treated wood supported a lower fraction of strongly adhering cells (1.87 ± 1.24 log CFU/cm2) versus untreated wood (3.72 ± 0.67 log CFU/cm2). L. monocytogenes demonstrated significant declines in strongly attaching cells during extended exposure to silane-treated wood, from 7.59 ± 0.14 to 5.27 ± 0.68 log CFU/cm2 over 8 h post-inoculation. Microscopic analysis demonstrated silane treatment increased the surface roughness of both woods, leading to superhydrophobic conditions on wood surfaces, consequently decreasing strong attachment of pathogenic bacteria.

Promoting neurovascularized bone regeneration with a novel 3D printed inorganic-organic magnesium silicate/PLA composite scaffold.

Critical-size bone defect repair presents multiple challenges, such as osteogenesis, vascularization, and neurogenesis. Current biomaterials for bone repair need more consideration for the above functions. Organic-inorganic composites combined with bioactive ions offer significant advantages in bone regeneration. In our work, we prepared an organic-inorganic composite material by blending polylactic acid (PLA) with 3-aminopropyltriethoxysilane (APTES)-modified magnesium silicate (A-M2S) and fabricated it by 3D printing. With the increase of A-M2S proportion, the hydrophilicity and mineralization ability showed an enhanced trend, and the compressive strength and elastic modulus were increased from 15.29 MPa and 94.61 MPa to 44.30 MPa and 435.77 MPa, respectively. Furthermore, A-M2S/PLA scaffolds not only exhibited good cytocompatibility of bone marrow mesenchymal stem cells (BMSCs), human umbilical vein endothelial cells (HUVECs), and Schwann cells (SCs), but also effectively promoted osteogenesis, angiogenesis, and neurogenesis in vitro. After implanting 10% A-M2S/PLA scaffolds in vivo, the scaffolds showed the most effective repair of cranium defects compared to the blank and control group (PLA). Additionally, they promoted the secretion of proteins related to bone regeneration and neurovascular formation. These results provided the basis for expanding the application of A-M2S and PLA in bone tissue engineering and presented a novel concept for neurovascularized bone repair.

Initial bone tissue reactions of hydroxyapatite/collagen-(3-glycidoxypropyl)trimethoxysilane injectable bone paste.

We have previously reported that a novel bioresorbable self-setting injectable bone paste composed of hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) and (3-glycidoxypropyl)trimethoxysilane (GPTMS) was successfully prepared and was replaced with new bone within 3 months of implantation in defects created in porcine tibia. In this study, the HAp/Col-GPTMS paste was implanted into bone defects in rat tibiae to investigate the initial kinetics and bone tissue response. Even though more than 35% of GPTMS molecules should be eluted rapidly from directly injected pastes according to previously reported cell culture tests, in this study, energy-dispersive X-ray spectrometry did not detect Si (GPTMS) deposition in tissues surrounding the paste at 1 day postimplantation. Further, no abnormal inflammatory responses were observed in the surrounding tissues over the test period for both directly injected and prehardened pastes. Companying these observations with the results of the previous animal test (in which the paste was fully resorbed and was substituted with new bone), the eluted GPTMS resolved in no harm in vivo from the initial to final (completely resorbed) stages. Material resorption rates calculated from X-ray microcomputed tomography (µ-CT) images decreased with increasing in GPTMS concentration. Histological observations indicated that tartrate-resistant acid phosphatase (TRAP) active cells, (assumed to be osteoclasts), exist on the periphery of pastes. This result suggested that the paste was resorbed by osteoclasts in the same way as the HAp/Col. Since a good correlation was observed between TRAP active areas in histological sections and material resorption rate calculated from µ-CT, the TRAP activity coverage ratio offers the possibility to estimate the osteoclastic resorption ratio of materials, which are replaced with bone via bone remodeling process.

Targetable domains for the design of peptide-dendrimer inhibitors of SARS-CoV-2.

We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of the main targets of world research. Based on the knowledge of the complex mechanism of viral infection we designed peptide-dendrimer inhibitors of SARS-CoV-2with the aim to block cell infection through interfering with the host-pathogen interactions. We used two different strategies: i) the first one aims at hindering the virus anchorage to the human cell; ii) the second -strategy points to interfere with the mechanism of virus-cell membrane fusion. We propose the use of different nanosized carriers, formed by several carbosilane dendritic wedges to deliver two different peptides designed to inhibit host interaction or virus entry. The antiviral activity of the peptide-dendrimers, as well as of free peptides and free dendrimers was evaluated through the use of SARS-CoV-2 pseudotyped lentivirus. The results obtained show that peptides designed to block host-pathogen interaction represent a valuable strategy for viral inhibition.

Ionic Liquid-Based Silane for SiO2 Nanoparticles: A Versatile Coupling Agent for Dental Resins.

The current longevity of dental resins intraorally is limited by susceptibility to acidic attacks from bacterial metabolic byproducts and vulnerability to enzymatic or hydrolytic degradation. Here, we demonstrate synthesizing an ionic liquid-based antibiofilm silane effective against Streptococcus mutans, a major caries pathogen. Furthermore, we incorporate this silane into dental resins, creating antibiofilm- and degradation-resistant materials applicable across resin types. FTIR, UV-vis, and NMR spectroscopy confirmed the synthesis of the expected ionic liquid-based silane. The characterization of SiO2 after the silanization indicated the presence of the silane and how it interacted with the oxide. All groups achieved a degree of conversion similar to that found for commercial resin composites immediately and after two months of storage in water. The minimum of 2.5 wt % of silane led to lower softening in solvent than the control group (GCTRL) (p < 0.05). While the flexural strength indicated a lower value from 1 wt % of silane compared to GCTRL (p < 0.05), the ultimate tensile strength did not indicate differences among groups (p > 0.05). There was no difference within groups between the immediate and long-term tests of flexural strength (p > 0.05) or ultimate tensile strength (p > 0.05). The addition of at least 5 wt % of silane reduced the viability of S. mutans compared to GCTRL (p < 0.05). The fluorescence microscopy analysis suggested that the higher the silane concentration, the higher the amount of bacteria with membrane defects. There was no difference among groups in the cytotoxicity test (p > 0.05). Therefore, the developed dental resins displayed biocompatibility, proper degree of conversion, improved resistance against softening in solvent, and stability after 6 months of storage in water. This material could be further developed to produce polymeric antimicrobial layers for different surfaces, supporting various potential avenues in developing novel biomaterials with enhanced therapeutic characteristics using ionic liquid-based materials.

A Novel Coated Suture Displays Antimicrobial Activity Without Compromising Structural Properties.

BACKGROUND: Treated or coated sutures promise to prevent contamination of wounds. PURPOSE: The purpose of the study was to coat surgical sutures with a new quaternary ammonium silane (QAS) antimicrobial compound at two different application temperatures and then to evaluate the resulting structural, physical, mechanical, and biological properties. STUDY DESIGN, SETTING, SAMPLE: In vitro and in vivo studies were conducted using male albino Wistar rats approved by the Joint Ethical Committee of IMU and Postgraduate Medical Institute, Lahore. Only suture samples, coated uniformly with verified presence of the compound and of adequate length were used. Samples which were not coated uniformly and with inadequate length or damaged were excluded. PREDICTOR VARIABLE: Predictor variables were sutures with and without QAS coatings and different temperatures. Sutures were coated with QAS at 0.5 and 1.0% wt/vol using the dip coating technique and sutures with and without QAS coating were tested at 25 and 40 °C temperatures. MAIN OUTCOME VARIABLE(S): Outcome variables of structural and physico-mechanical properties of QAS-coated and non-coated sutures were measured using Fourier transform infrared spectroscopy (for structural changes), confocal laser and scanning electron (for diameter changes), and tensile strength/modulus (for mechanical testing). Biologic outcome variables were tested (bacterial viability); macrophage cultures from Wistar rats were tested (M1/M2 polarization detecting IL-6 and IL-10). Macrophage cells were analyzed with CD80+ (M1) and CD163+ (M2). Chemotaxis index was calculated as a ratio of quantitative fluorescence of cells. COVARIATES: Not applicable. ANALYSES: Ordinal data among groups were compared using the Wilcoxon Mann-Whitney U test along with the comparison of histological analysis using the Wilcoxon Sign-rank test (P < .05). RESULTS: Fourier transform infrared spectroscopy peak at 1490 cm-1 confirmed the presence of QAS on suture's surfaces with a significant increase (P < .05) in diameter (0.99 ± 0.5-mm) and weight (0.77 ± 0.02-mg) observed for 1% QAS groups treated at 40 °C. Non-coated samples heated at 25 °C had significantly (P < .05) less diameters (0.22 ± 0.03-mm) and weights (0.26 ± 0.06-mg). Highest tensile strength/modulus was observed for 0.5% QAS-coated samples which also had significantly higher antibacterial characteristics than other sutures (P < .05). QAS-coated sutures significantly increased M1 and M2 markers. CONCLUSION AND RELEVANCE: QAS coating conferred antibacterial action properties without compromising the physical and mechanical properties of the suture.

Enhancing antibacterial properties of titanium implants through a novel Ag-TiO2-OTS nanocomposite coating: a comprehensive study on resist-killing-disintegrate approach.

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO2-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants.

Generalized Multifunctional Coating Strategies Based on Polyphenol-Amine-Inspired Chemistry and Layer-by-Layer Deposition for Blood Contact Catheters.

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.

Promising Anticancer Prodrugs Based on Pt(IV) Complexes with Bis-organosilane Ligands in Axial Positions.

We report two novel prodrug Pt(IV) complexes with bis-organosilane ligands in axial positions: cis-dichloro(diamine)-trans-[3-(triethoxysilyl)propylcarbamate]platinum(IV) (Pt(IV)-biSi-1) and cis-dichloro(diisopropylamine)-trans-[3-(triethoxysilyl) propyl carbamate]platinum(IV) (Pt(IV)-biSi-2). Pt(IV)-biSi-2 demonstrated enhanced in vitro cytotoxicity against colon cancer cells (HCT 116 and HT-29) compared with cisplatin and Pt(IV)-biSi-1. Notably, Pt(IV)-biSi-2 exhibited higher cytotoxicity toward cancer cells and lower toxicity on nontumorigenic intestinal cells (HIEC6). In preclinical mouse models of colorectal cancer, Pt(IV)-biSi-2 outperformed cisplatin in reducing tumor growth at lower concentrations, with reduced side effects. Mechanistically, Pt(IV)-biSi-2 induced permanent DNA damage independent of p53 levels. DNA damage such as double-strand breaks marked by histone gH2Ax was permanent after treatment with Pt(IV)-biSi-2, in contrast to cisplatin's transient effects. Pt(IV)-biSi-2's faster reduction to Pt(II) species upon exposure to biological reductants supports its superior biological response. These findings unveil a novel strategy for designing Pt(IV) anticancer prodrugs with enhanced activity and specificity, offering therapeutic opportunities beyond conventional Pt drugs.

Development of an antimicrobial, 3D printable denture base material with K18 quaternary ammonium silane-functionalized methyl methacrylate and filler.

STATEMENT OF PROBLEM: Denture base materials are highly susceptible to microbial colonization, which can lead to denture stomatitis. In addition, patients who sleep with their dentures have an increased chance of contracting pneumonia. Commercially available antimicrobial denture base materials to prevent or combat microbial colonization are lacking. PURPOSE: The purpose of this in vitro study was to determine the effects of K18 quaternary ammonium methacryloxy silane-functionalized filler (K18-Filler) and methyl methacrylate (K18-MMA) on the polymerization of 3D printed denture base material and its esthetic, mechanical, and antimicrobial properties. MATERIAL AND METHODS: K18-Filler (0%, 10%, 20% w/w) and K18-MMA (0%, 5%, 12.5% w/w) were added to a 3D printable denture base resin (Denture Base Resin, Original Pink; Formlabs Inc) and 3D printed. Specimens were tested by using the Rockwell15T hardness, near infrared FTIR monomer-to-polymer degree of conversion (DoC), transparency parameter (TP), color shift, and 3-point bend and by counting colony forming units against Streptococcus aureus, Streptococcus sanguinis and Candida albicans tests. Data were analyzed using analysis of variance with the Tukey-Kramer HSD post hoc test. RESULTS: Control resins had significantly higher Rockwell15T hardness than most of the K18 groups (P<.05) but had comparable DoC with all K18 groups except one, showing that all groups were well polymerized. Controls had significantly higher TP than most K18 groups, but most K18 groups had ΔE<3.3, so the color shift was not noticeable. However, the 12.5% K18-MMA with 10% and 20% K18-Filler groups, which were also the groups used to test for antimicrobial activity, had ΔE>8. All K18 groups had comparable or greater moduli than the controls, but the controls had significantly higher ultimate transverse strengths than most K18 groups (P<.05). All 12.5% K18-MMA with K18-Filler groups had significant antimicrobial activity against S. aureus, S. sanguinis, and C. albicans. CONCLUSIONS: 12.5% K18-MMA and K18-Filler produced 3D printable denture materials with comparable polymerization properties and significant antimicrobial properties against S. mutans, S. sanguinis, and C. albicans. High K18-MMA and K18-Filler concentrations caused significant color shifts and reductions in ultimate strengths.

Effects of silica surface modification with silane and poly(ethylene glycol) on flexural strength, protein-repellent, and antibacterial properties of acrylic dental nanocomposites.

OBJECTIVE: The main aim of the current work was to develop dental acrylic-based composites with protein-repellent and antibacterial properties by using surface-modified silica nanoparticles. The effects of surface modification of silica nanoparticles in protein-repellent and antibacterial activity and mechanical properties of dental composites including flexural strength, flexural modulus, and hardness were discussed. METHODS: The surface of silica nanoparticles was first chemically treated with 3-methacryloxypropyltrimethoxysilane (MPS) as a coupling agent and then with poly(ethylene glycol) (PEG) bonded to MPS. Dental acrylic-based composites were prepared with mass fractions of 10, 15, 20, 30, and 40 % of PEG-modified MPS-silica nanoparticles (PMS). The chemical surface modification of silica nanoparticles with MPS and PEG was confirmed by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). RESULTS: The dental composite containing 20 wt% PMS nanoparticles could reduce the protein adsorption by 28 % as compared with a composite containing 20 wt% MPS-modified silica. The antibacterial test indicated that the PMS nanoparticles can significantly reduce the adhesion of Streptococcus mutans and the biofilm formation on the surface of dental composites. It was found that the flexural strength increased by increasing the PMS nanoparticles from 0 to 20 wt% and then decreased by the incorporation of higher percentages of these nanoparticles. Also, with increasing the weight percentage of PMS nanoparticles, the elastic and the flexural modulus and the hardness of resin nanocomposites were increased. SIGNIFICANCE: In the current work, for the first time, dental resin composites containing PEG were prepared with excellent protein-repellent and antibacterial properties.

Biocompatible silane adhesion layer on titanium implants improves angiogenesis and osteogenesis.

Silane adhesion layer strategy has been widely used to covalently graft biomolecules to the titanium implant surface, thereby conferring the implant bioactivity to ameliorate osseointegration. However, few researchers pay attention to the effects of silanization parameters on biocompatibility and biofunctionality of the silane adhesion layers. Accordingly, the present study successfully fabricated the silane adhesion layers with different thickness, intactness, and surface morphologies by introducing 3-aminopropyltriethoxysilane on the alkali-treated titanium surface in time-varied processing of silanization. The regulatory effects of the silane adhesion layers on angiogenesis and osteogenesis were assessed in vitro. Results showed that the prolonged silanization processing time increased the thickness and intactness of the silane adhesion layer and significantly improved its biocompatibility. Notably, the silane adhesion layer prepared after 12 h of silanization exhibited a brain-like surface morphology and benefited the adhesion and proliferation of endothelial cells (ECs) and osteoblasts (OBs). Moreover, the layer promoted angiogenesis via stimulating vascular endothelial growth factor (VEGF) secretion and nitric oxide (NO) production of ECs. Simultaneously, it improved osteogenesis by enhancing alkaline phosphatase (ALP) activity, collagen secretion, and extracellular matrix mineralization of OBs. This work systematically investigated the biocompatibility and biofunctionality of the modified silane adhesion layers, thus providing valuable references for their application in covalently grafting biomolecules on the titanium implant surface.

A Lysosome-Targeting Self-Condensation Prodrug-Nanoplatform System for Addressing Drug Resistance of Cancer.

Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.

Biochemical changes and macrophage polarization of a silane-based endodontic irrigant in an animal model.

Silane-based/fully hydrolyzed, endodontic irrigant exhibiting antimicrobial properties, is prepared, and is hypothesized to control macrophage polarization for tissue repair. Albino wistar rats were injected with 0.1 ml root canal irrigant, and bone marrow cells procured. Cellular mitochondria were stained with MitoTracker green along with Transmission Electron Microscopy (TEM) performed for macrophage extracellular vesicle. Bone marrow stromal cells (BMSCs) were induced for M1 and M2 polarization and Raman spectroscopy with scratch assay performed. Cell counting was used to measure cytotoxicity, and fluorescence microscopy performed for CD163. Scanning Electron Microscopy (SEM) was used to investigate interaction of irrigants with Enterococcus faecalis. K21 specimens exhibited reduction in epithelium thickness and more mitochondrial mass. EVs showed differences between all groups with decrease and increase in IL-6 and IL-10 respectively. 0.5%k21 enhanced wound healing with more fibroblastic growth inside scratch analysis along with increased inflammation-related genes (ICAM-1, CXCL10, CXCL11, VCAM-1, CCL2, and CXCL8; tissue remodelling-related genes, collagen 1, EGFR and TIMP-2 in q-PCR analysis. Sharp bands at 1643 cm-1 existed in all with variable intensities. 0.5%k21 had a survival rate of BMSCs comparable to control group. Bacteria treated with 0.5%k21/1%k21, displayed damage. Antimicrobial and reparative efficacy of k21 disinfectant is a proof of concept for enhanced killing of bacteria across root dentin acquiring functional type M2 polarization for ethnopharmacological effects.

Triazine-Carbosilane Dendrimersomes Enhance Cellular Uptake and Phototoxic Activity of Rose Bengal in Basal Cell Skin Carcinoma Cells.

Background: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem. Methods: Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and H2DCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy). Results: Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer. Conclusion: Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.

The Antibacterial Effect of PEGylated Carbosilane Dendrimers on P. aeruginosa Alone and in Combination with Phage-Derived Endolysin.

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin-CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.

Induction of resistance of Podosphaera xanthii (hull-less pumpkin powdery mildew) to triazole fungicides and its resistance mechanism.

The aim of this study was to uncover the molecular mechanism through which fungicide resistance develops in Podosphaera xanthii, a fungi that causes powdery mildew in hull-less pumpkin. Treatments of inoculated P. xanthii were carried out on leaves of hull-less pumpkin and subsequently treated with kinds of triazole fungicide for seven generations. Resistant strains of P. xanthii thus obtained were evaluated for their resistance levels. The resistance levels of the fungi to four fungicides of were high except that of the propiconazole-resistant strain, which showed moderate resistance. The F7 generations of five resistant strains thus obtained were cultured continuously for five generations without fungicide induction, and their resistance level were found to be relatively stable. The DNA of the sensitive strain and the five kinds of resistant strains were extracted by the sodium dodecyl sulfate (SDS) method and its internal transcribed spacer (ITS) region was amplified by using ITS1/ITS4 primer and specific primer F/R and they were sequenced respectively. The DNA sequence comparison of resistant and sensitive strains showed that the base pairs of tebuconazole-resistant strains and flusilazole-resistant strains were mutated, with mutation rates of 4.8% and 1.6%, respectively. The base pairs of the other three resistant strains did not change.

Sol-gel-derived hard coatings from tetraethoxysilane and organoalkoxysilanes bearing zwitterionic and isothiazolinone groups and their antifouling behaviors.

Current environmentally friendly marine antifouling (AF) coatings are mainly polymeric with a relatively low hardness. Hard sol-gel-derived AF coatings for underwater robot-cleaning are seldom used. In this work, two new organoalkoxysilanes, i.e., (N-methoxyacylethyl)-3-aminopropyltriethoxysilane and 2-(2-hydroxy-3-(3-(trimethoxysilyl)propoxy)propyl)benzo[d]isothiazol-3(2H)-one, were synthesized by a facile method. These two precursors were used with tetraethoxysilane (TEOS) to produce three series of hybrid AF coatings with zwitterionic group (Z-χ), antibacterial group (1,2-benzisothiazolin-3-one) (A-χ) and zwitterionic and antibacterial groups (S-χ) by a sol-gel process. The hardness of the coatings was measured using a pencil hardness tester and the AF behaviors of the coatings were examined by laboratory and field assays. A pencil hardness up to 5 H was achieved and slight deterioration was observed after 9 months of immersion in artificial seawater for the A-χ and S-χ coatings at a sufficiently high TEOS content. A synergistic effect between the zwitterion and antimicrobial agents existed but was not obvious. A higher TEOS content led to a higher hardness and better AF performance regardless of the type of AF group. Even with the same biofilm formation after field assay, coatings with a higher TEOS content exhibited a better resistance to mussel settlement.