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1.
ACS Biomater Sci Eng ; 10(5): 3057-3068, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38641433

ABSTRACT

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.


Subject(s)
Catheters , Coated Materials, Biocompatible , Heparin , Polyphenols , Tannins , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Humans , Catheters/microbiology , Polyphenols/chemistry , Polyphenols/pharmacology , Heparin/chemistry , Heparin/pharmacology , Tannins/chemistry , Tannins/pharmacology , Silanes/chemistry , Silanes/pharmacology , Anticoagulants/chemistry , Anticoagulants/pharmacology , Propylamines/chemistry , Amines/chemistry , Amines/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polylysine/chemistry , Polylysine/pharmacology , Surface Properties , Hydrophobic and Hydrophilic Interactions , Human Umbilical Vein Endothelial Cells/drug effects , Silicone Elastomers/chemistry , Adsorption , Escherichia coli/drug effects
2.
J Med Chem ; 67(8): 6410-6424, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38592014

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Organoplatinum Compounds , Prodrugs , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/chemical synthesis , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Ligands , Mice , Cell Line, Tumor , Silanes/chemistry , Silanes/pharmacology , Structure-Activity Relationship , Drug Screening Assays, Antitumor , HT29 Cells
3.
J Prosthet Dent ; 131(6): 1251.e1-1251.e8, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38523046

ABSTRACT

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.


Subject(s)
Dental Materials , Denture Bases , Methylmethacrylate , Printing, Three-Dimensional , Quaternary Ammonium Compounds , Silanes , Denture Bases/microbiology , Methylmethacrylate/chemistry , Silanes/chemistry , Silanes/pharmacology , Quaternary Ammonium Compounds/pharmacology , Quaternary Ammonium Compounds/chemistry , Dental Materials/chemistry , Anti-Infective Agents/pharmacology , Materials Testing , Polymerization , In Vitro Techniques , Humans , Candida albicans/drug effects
4.
Dent Mater ; 39(10): 863-871, 2023 10.
Article in English | MEDLINE | ID: mdl-37550139

ABSTRACT

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.


Subject(s)
Flexural Strength , Nanocomposites , Polyethylene Glycols/pharmacology , Polyethylene Glycols/chemistry , Composite Resins/pharmacology , Composite Resins/chemistry , Polymethacrylic Acids/chemistry , Silicon Dioxide/pharmacology , Silicon Dioxide/chemistry , Silanes/pharmacology , Silanes/chemistry , Pliability , Materials Testing , Nanocomposites/chemistry , Anti-Bacterial Agents/pharmacology , Surface Properties
5.
Biomater Adv ; 139: 213033, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35882124

ABSTRACT

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.


Subject(s)
Osteogenesis , Titanium , Endothelial Cells , Silanes/pharmacology , Surface Properties , Titanium/pharmacology , Vascular Endothelial Growth Factor A/pharmacology
6.
Nano Lett ; 22(10): 3983-3992, 2022 05 25.
Article in English | MEDLINE | ID: mdl-35548949

ABSTRACT

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.


Subject(s)
Nanoparticles , Neoplasms , Prodrugs , Cell Line, Tumor , Drug Resistance , Humans , Lysosomes/pathology , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Neoplasms/pathology , Prodrugs/pharmacology , Prodrugs/therapeutic use , Silanes/pharmacology , Silanes/therapeutic use
7.
Sci Rep ; 12(1): 6354, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35428859

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Silanes , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Biofilms , Dentin , Enterococcus faecalis , Macrophages , Models, Animal , Root Canal Irrigants/pharmacology , Silanes/pharmacology , Sodium Hypochlorite/pharmacology
8.
Int J Nanomedicine ; 17: 1139-1154, 2022.
Article in English | MEDLINE | ID: mdl-35321027

ABSTRACT

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.


Subject(s)
Carcinoma , Rose Bengal , Humans , Rose Bengal/chemistry , Rose Bengal/pharmacology , Silanes/pharmacology , Triazines/pharmacology
9.
PLoS One ; 17(2): e0263068, 2022.
Article in English | MEDLINE | ID: mdl-35104292

ABSTRACT

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.


Subject(s)
Antifungal Agents/pharmacology , Ascomycota/genetics , Drug Resistance, Fungal/drug effects , Plant Diseases/microbiology , Triazoles/pharmacology , Ascomycota/physiology , Cucurbita/genetics , Cucurbita/microbiology , Drug Resistance, Fungal/genetics , Plant Diseases/genetics , Plant Leaves/genetics , Plant Leaves/microbiology , Silanes/pharmacology
10.
Int J Mol Sci ; 23(3)2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35163794

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Endopeptidases/pharmacology , Polyethylene Glycols/chemistry , Pseudomonas aeruginosa/growth & development , Silanes/pharmacology , Anti-Bacterial Agents/chemistry , Bacteriophages/metabolism , Biofilms/drug effects , Dendrimers , Drug Compounding , Drug Synergism , Interferometry , Microbial Sensitivity Tests , Microbial Viability/drug effects , Microscopy, Fluorescence , Plankton/drug effects , Pseudomonas aeruginosa/drug effects , Silanes/chemistry
11.
J Mater Chem B ; 10(3): 406-417, 2022 01 19.
Article in English | MEDLINE | ID: mdl-34935850

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofouling/prevention & control , Gels/pharmacology , Silanes/pharmacology , Thiazoles/pharmacology , Adhesiveness , Adsorption/drug effects , Animals , Anti-Bacterial Agents/chemical synthesis , Bacteria/drug effects , Bivalvia/drug effects , Diatoms/drug effects , Gels/chemical synthesis , Microbial Sensitivity Tests , Proteins/chemistry , Seawater/microbiology , Silanes/chemical synthesis , Thiazoles/chemical synthesis
12.
ACS Appl Mater Interfaces ; 13(39): 46938-46950, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-34559507

ABSTRACT

Smart response hydrogel has a broad application prospect in human health real-time monitoring due to its responses to a variety of stimuli. In this study, we developed a novel smart hydrogel dressing based on conductive MXene nanosheets and a temperature-sensitive PNIPAm polymer. γ-Methacryloxypropyltrimethoxysilane (KH570) was selected to functionalize the surface of MXene further to improve the interface compatibility between MXene and PNIPAm. Our prepared K-M/PNIPAm hydrogel was found to have a strain-sensitive property, as well as a respond to NIR phase change and volume change. When applied as a strain flexible sensor, this K-M/PNIPAm hydrogel exhibited a high strain sensitivity with a gauge factor (GF) of 4.491, a broad working strain range of ≈250%, a fast response of ∼160 ms, and good cycle stability (i.e., 3000 s at 20% strain). Besides, this K-M/PNIPAm hydrogel can be used as an efficient NIR light-controlled drug release carrier to achieve on-demand drug release. This work paved the way for the application of smart response hydrogel in human health real-time monitoring and NIR-controlled drug release functions.


Subject(s)
Drug Carriers/chemistry , Hydrogels/chemistry , Smart Materials/chemistry , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Acrylic Resins/radiation effects , Acrylic Resins/toxicity , Animals , Cell Line , Drug Carriers/pharmacology , Drug Carriers/radiation effects , Drug Carriers/toxicity , Drug Liberation/radiation effects , Elasticity , Hydrogels/pharmacology , Hydrogels/radiation effects , Hydrogels/toxicity , Infrared Rays , Male , Methacrylates/chemistry , Methacrylates/pharmacology , Methacrylates/radiation effects , Methacrylates/toxicity , Mice , Rats, Sprague-Dawley , Silanes/chemistry , Silanes/pharmacology , Silanes/radiation effects , Silanes/toxicity , Skin/drug effects , Smart Materials/pharmacology , Smart Materials/radiation effects , Smart Materials/toxicity , Stress, Mechanical , Tetracycline/chemistry , Titanium/chemistry , Titanium/pharmacology , Titanium/radiation effects , Titanium/toxicity , Wound Healing/drug effects
13.
Int J Mol Sci ; 22(16)2021 Aug 04.
Article in English | MEDLINE | ID: mdl-34445073

ABSTRACT

Human immunodeficiency virus (HIV-1) is still a major problem, not only in developing countries but is also re-emerging in several developed countries, thus the development of new compounds able to inhibit the virus, either for prophylaxis or treatment, is still needed. Nanotechnology has provided the science community with several new tools for biomedical applications. G2-S16 is a polyanionic carbosilane dendrimer capable of inhibiting HIV-1 in vitro and in vivo by interacting directly with viral particles. One of the main barriers for HIV-1 eradication is the reservoirs created in primoinfection. These reservoirs, mainly in T cells, are untargetable by actual drugs or immune system. Thus, one approach is inhibiting HIV-1 from reaching these reservoir cells. In this context, macrophages play a main role as they can deliver viral particles to T cells establishing reservoirs. We showed that G2-S16 dendrimer is capable of inhibiting the infection from infected macrophages to healthy T CD4/CD8 lymphocytes by eliminating HIV-1 infectivity inside macrophages, so they are not able to carry infectious particles to other body locations, thus preventing the reservoirs from forming.


Subject(s)
Alkanesulfonates/pharmacology , Anti-HIV Agents/pharmacology , Dendrimers/pharmacology , HIV Infections/drug therapy , HIV-1/drug effects , Macrophages/drug effects , Organosilicon Compounds/pharmacology , Silanes/pharmacology , Cell Line , Cells, Cultured , HIV Infections/transmission , Humans , Macrophages/virology , Polyelectrolytes/pharmacology
14.
Int J Mol Sci ; 22(13)2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34281151

ABSTRACT

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.


Subject(s)
RNA, Small Interfering/therapeutic use , Silanes/pharmacology , Cations , Cell Survival , Circular Dichroism , Dendrimers/chemistry , Dendrimers/pharmacology , Genetic Therapy/methods , Humans , MCF-7 Cells , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Particle Size , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Double-Stranded/genetics , RNA, Small Interfering/genetics , Silanes/chemistry , Silanes/metabolism
15.
J Nanobiotechnology ; 19(1): 65, 2021 Mar 03.
Article in English | MEDLINE | ID: mdl-33658029

ABSTRACT

BACKGROUND: Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. RESULTS: We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1-50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. CONCLUSIONS: Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.


Subject(s)
Antiviral Agents/pharmacology , Cytomegalovirus Infections/drug therapy , Cytomegalovirus/drug effects , Dendrimers/pharmacology , Nanotechnology/methods , Silanes/pharmacology , Anti-HIV Agents/pharmacology , Cell Line , Fibroblasts , Ganciclovir , HIV Infections , HIV-1 , Humans , Polyelectrolytes
16.
Eur J Med Chem ; 215: 113292, 2021 Apr 05.
Article in English | MEDLINE | ID: mdl-33631696

ABSTRACT

Iminopyridine-decorated carbosilane metallodendrimers have recently emerged as a promising strategy in the treatment of cancer diseases. Their unique features such as the nanometric size, the multivalent nature and the structural perfection offer an extraordinary platform to explore structure-to-property relationships. Herein, we showcase the outstanding impact on the antitumor activity of a parameter not explored before: the iminopyridine substituents in meta position. New Cu(II) carbosilane metallodendrimers, bearing methyl or methoxy substituents in the pyridine ring, were synthesized and thoroughly characterized. Electron Paramagnetic Resonance (EPR) was exploited to unveil the properties of the metallodendrimers. This study confirmed the presence of different coordination modes of the Cu(II) ion (Cu-N2O2, Cu-N4 and Cu-O4), whose ratios were determined by the structural features of the dendritic molecules. These metallodendrimers exhibited IC50 values in the low micromolar range (<6 µM) in tumor cell lines such as HeLa and MCF-7. The subsequent in vitro assays on both healthy (PBMC) and tumor (U937) myeloid cells revealed two key facts which improved the cytotoxicity and selectivity of the metallodrug: First, maximizing the Cu-N2O2 coordination mode; second, adequately selecting the pair ring-substituent/metal-counterion. The most promising candidates, G1(-CH3)Cl (8) and G1(-OCH3)NO3(17), exhibited a substantial increase in the antitumor activity in U937 tumor cells, compared to the non-substituted counterparts, probably through two different ROS-production pathways.


Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , Dendrimers/pharmacology , Pyridines/pharmacology , Silanes/pharmacology , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Line, Tumor , Coordination Complexes/chemical synthesis , Copper/chemistry , Dendrimers/chemical synthesis , Drug Screening Assays, Antitumor , Humans , Leukocytes, Mononuclear/drug effects , Mitochondria/drug effects , Pyridines/chemical synthesis , Reactive Oxygen Species/metabolism , Silanes/chemical synthesis
17.
J Biomed Mater Res A ; 109(5): 754-765, 2021 05.
Article in English | MEDLINE | ID: mdl-32681740

ABSTRACT

Bioprosthetic heart valve (BHV) replacement is increasingly used for treating valve-related diseases worldwide but the current commercially used BHVs treated with glutaraldehyde (Glut) often failed within 12-15 years due to degradation, thrombosis, inferior biocompatibility, and calcification. Herein, 3-glycidyloxypropyl trimethoxysilane (GPTMS) was used to crosslink porcine pericardium (PP) at the concentration (vol/vol) of 0.25%, 1%, 2%, and 4% and their performance for potential application in BHVs was evaluated. The crosslinking mechanism mainly involved the ring-opening of epoxide by amine attack and silanol poly-condensation. The stability of collagen in higher concentration (1%, 2%, and 4%) GPTMS crosslinked PPs (GPTMS-PPs) was clearly increased. GPTMS-PPs showed no cytotoxicity and supported the growth of endothelial cells while Glut-PP did not. GPTMS-PPs were less prothrombotic than Glut-PP. GPTMS-PP crosslinked at 1% concentration showed comparable mechanical properties to Glut-PP while had better anti-tearing performance. The subcutaneous implantation in rat for 30 days showed that GPTMS crosslinking was able to effectively inhibit the calcification of BHV.


Subject(s)
Biocompatible Materials/chemistry , Bioprosthesis , Heart Valve Prosthesis , Animals , Biocompatible Materials/toxicity , Blood Coagulation , Calcinosis/chemically induced , Calorimetry, Differential Scanning , Cell Line , Collagen/chemistry , Cross-Linking Reagents , Epoxy Compounds/pharmacology , Fibroblasts , Glutaral/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Implants, Experimental , Male , Materials Testing , Mice , Microscopy, Electron, Scanning , Pericardium , Polymerization , Rats , Rats, Sprague-Dawley , Silanes/pharmacology , Siloxanes , Spectroscopy, Fourier Transform Infrared , Tensile Strength
18.
ACS Appl Bio Mater ; 4(3): 2385-2397, 2021 03 15.
Article in English | MEDLINE | ID: mdl-35014359

ABSTRACT

Polyelectrolyte multilayer (PEM) assembly is a versatile tool to construct low-fouling coatings. For application in the marine environment, their structure needs to be stabilized by covalent linkage. Here, we introduce an approach for spin coating of silane-based sol-gel chemistries using layer-by-layer assembly of polysaccharide-based hybrid polymer coatings (LBLHPs). The silane sol-gel chemistry allows the films to be cross-linked under water-based and mild reaction conditions. Two different silanes were used for this purpose, a conventional triethoxymethyl silane and a de novo synthesized zwitterionic silane. The polysaccharide-silane hybrid polymer coatings were thoroughly characterized with spectroscopic ellipsometry, water contact angle (WCA) goniometry, attenuated total reflection-Fourier transform infrared spectroscopy, and atomic force microscopy. The coatings showed good stability in seawater, smooth surfaces, a high degree of hydration, and WCAs below or close to the Berg limit. LBLHPs showed low-fouling properties in biological assays against nonspecific protein adsorption, attachment of the diatom Navicula perminuta, and settlement of zoospores of the macroalga Ulva linza.


Subject(s)
Biofouling/prevention & control , Coated Materials, Biocompatible/pharmacology , Diatoms/drug effects , Polysaccharides/pharmacology , Silanes/pharmacology , Ulva/drug effects , Carbohydrate Conformation , Coated Materials, Biocompatible/chemistry , Materials Testing , Particle Size , Polysaccharides/chemistry , Silanes/chemistry
19.
J Biomater Appl ; 35(8): 1019-1033, 2021 03.
Article in English | MEDLINE | ID: mdl-33290123

ABSTRACT

Tacrolimus (TAC), a potent immunosuppressive macrolide, has been investigated for ocular diseases due to promising results in the treatment of anterior and posterior segments eye diseases. Mesoporous and functionalized silica nanoparticles show potential as TAC delivery platforms owing to their interesting characteristic as large surface area, uniform pore size distribution, high pore volume, and excellent biocompatibility. The purpose of this study was to incorporate TAC in functionalized silica nanoparticles with 3-aminopropyltriethoxysilane (MSNAPTES) and investigate the safety and biocompatibility of the systems. The MSNAPTES and MSNAPTES TAC nanoparticles were characterized. The in vitro cytotoxicity of MSNAPTES and MSNAPTES load with TAC (MSNAPTES-TAC) in retinal pigment epithelial cells (ARPE-19) was determined, chorioallantoic membrane (CAM) assay model was used to investigate the in vivo biocompatibility, and safety of intravitreal injection was evaluated using clinical examination (assessment of intraocular pressure and indirect fundus ophthalmoscopy), electroretinographic (ERG) and histologic studies in rats' eyes. The elemental analysis (CHN), thermogravimetric (TGA), photon correlation spectroscopy and Fourier transform infrared (FTIR) analysis confirmed the presence of functionalized agent and TAC in the MSNAPTES nanoparticles. TAC loading was estimated at 7% for the MSNAPTES TAC nanoparticles. MSNAPTES and MSNAPTES TAC did not present in vitro cytotoxicity. The drug delivery systems showed good biocompatibility on CAM. No retinal abnormalities, vitreous hemorrhage, neovascularization, retinal detachment, and optic nerve atrophy were observed during the in vivo study. Follow-up ERGs showed no changes in the function of the retina cells after 15 days of intravitreal injection, and histopathologic observations support these findings. In conclusion, MSNAPTES TAC was successfully synthesized, and physicochemical analyses confirmed the presence of TAC in the nanoparticles. In vitro and in vivo studies indicated that MSNAPTES TAC was safe to intravitreal administration. Taking into account the enormous potential of MSNAPTES to carry TAC, this platform could be a promising strategy for TAC ocular drug delivery in the treatment of eye diseases.


Subject(s)
Nanoparticles/chemistry , Silicon Dioxide/chemistry , Tacrolimus/administration & dosage , Administration, Intravesical , Animals , Biocompatible Materials/administration & dosage , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line , Cell Survival/drug effects , Drug Delivery Systems , Humans , Nanoparticles/administration & dosage , Particle Size , Porosity , Propylamines/administration & dosage , Propylamines/chemistry , Propylamines/pharmacology , Rats , Silanes/administration & dosage , Silanes/chemistry , Silanes/pharmacology , Silicon Dioxide/administration & dosage , Silicon Dioxide/pharmacology , Tacrolimus/chemistry , Tacrolimus/pharmacology
20.
Int J Biol Macromol ; 163: 2457-2464, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-32980415

ABSTRACT

A novel cellulosic fibre was extracted from the peduncle portion of the fish tail palm tree and the extracted fish tail palm fibre was treated with different concentrations (1%, 5%, and 9%) of silane solution. The characteristic analysis on chemical, functional, mechanical and surface property of the extracted fish tail palm fibres were investigated through chemical composition analysis, Fourier Transform InfraRed spectroscopy (FT-IR), single fibre tensile test, and Scanning Electron Microscopy (SEM). Chemical analysis results indicate that silane treatment improved the cellulose content of the fish tail palm fibre. The highest cellulose content of 72.51% was observed in the 9% silane treated fish tail palm fibre. Also, it improved crystallinity index value of 62.5% for 5% silane treated fibre, which is confirmed through the X-ray diffraction analysis. FT-IR result indicates the removal of hemicellulose at characteristic wavelength of 1745 cm-1 for 5% silane treated fish tail palm fibre. Tensile property of the silane treated fish tail palm fibre (1, 5, and 9%) shows an increased tensile strength of 7.3%, 12%, and 6.6% as compared to raw fish tail palm fibre. Moreover, this type of novel natural fibres can reduce the cost while offering competent performance during the polymer-based product development.


Subject(s)
Arecaceae/chemistry , Cellulose/chemistry , Silanes/pharmacology , Arecaceae/drug effects , Microscopy, Electron, Scanning , Polymers/chemistry , Polysaccharides/chemistry , Silanes/chemistry , Spectroscopy, Fourier Transform Infrared , Tensile Strength/drug effects
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