ABSTRACT
To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m3. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m3-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m3-exposed females and were not statistically significant. However, the incidence in the 8 mg/m3-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m3-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.
Subject(s)
Inhalation Exposure , Lung Neoplasms , Rats, Inbred F344 , Titanium , Animals , Titanium/toxicity , Titanium/administration & dosage , Male , Lung Neoplasms/chemically induced , Lung Neoplasms/pathology , Female , Inhalation Exposure/adverse effects , Aerosols , Lung/pathology , Lung/drug effects , Nanoparticles/toxicity , RatsABSTRACT
Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 â â¢O2- and CO2 â CO) and three oxidation reactions (H2O â â¢OH, GSH â GSSG, and LA â PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.
Subject(s)
Barium Compounds , Biomimetic Materials , Colorectal Neoplasms , Immunosuppression Therapy , Nanotubes , Robotics , Titanium , Tumor Microenvironment , Veillonella , Biomimetic Materials/administration & dosage , Catalysis , Colorectal Neoplasms/drug therapy , Staphylococcus aureus , Nanotubes/chemistry , Titanium/administration & dosage , Titanium/pharmacology , Barium Compounds/administration & dosage , Barium Compounds/pharmacology , Cell Membrane/chemistry , Administration, Oral , Oxidation-Reduction , Immunosuppression Therapy/methods , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Lactic Acid/metabolism , Humans , Cell Line, TumorABSTRACT
Maternal inhalation exposure to engineered nanomaterials (ENM) has been associated with microvascular dysfunction and adverse cardiovascular responses. Pregnancy requires coordinated vascular adaptation and growth that are imperative for survival. Key events in pregnancy hallmark distinct periods of gestation such as implantation, spiral artery remodeling, placentation, and trophoblast invasion. Angiotensin II (Ang II) is a critical vasoactive mediator responsible for adaptations and is implicated in the pathology of preeclampsia. If perturbations occur during gestation, such as those caused by ENM inhalation exposure, then maternal-fetal health consequences may occur. Our study aimed to identify the period of gestation in which maternal microvascular functional and fetal health are most vulnerable. Additionally, we wanted to determine if Ang II sensitivity and receptor density is altered due to exposure. Dams were exposed to ENM aerosols (nano-titanium dioxide) during three gestational windows: early (EE, gestational day (GD) 2-6), mid (ME, GD 8-12) or late (LE, GD 15-19). Within the EE group dry pup mass decreased by 16.3% and uterine radial artery wall to lumen ratio (WLR) increased by 25.9%. Uterine radial artery response to Ang II sensitivity increased by 40.5% in the EE group. Ang II receptor density was altered in the EE and LE group with decreased levels of AT2R. We conclude that early gestational maternal inhalation exposures resulted in altered vascular anatomy and physiology. Exposure during this time-period results in altered vascular reactivity and changes to uterine radial artery WLR, leading to decreased perfusion to the fetus and resulting in lower pup mass.
Subject(s)
Angiotensin II/pharmacology , Metal Nanoparticles/toxicity , Microcirculation , Placental Circulation , Titanium/toxicity , Uterine Artery/drug effects , Vasoconstriction/drug effects , Aerosols , Animals , Estradiol/blood , Female , Gestational Age , Inhalation Exposure , Maternal Exposure , Metal Nanoparticles/administration & dosage , Pregnancy , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1/agonists , Receptor, Angiotensin, Type 1/metabolism , Titanium/administration & dosage , Uterine Artery/physiopathologyABSTRACT
PURPOSE: The aim of the present prospective study was to evaluate the effect of titanium mesh and concentrated growth factor (CGF) membranes in reconstructing severe labial bone defects during immediate implantation of anterior maxillary tooth. METHODS: Patients with severe defects presenting on the anterior labial bone plate of maxillary were enrolled in this study. During immediate implantation, the titanium mesh was used to maintain the space of bone graft, collagen membrane, and xenograft bone that were used to guide bone regeneration (GBR). Cone beam computed tomography (CBCT) was used to measure the height and the labial bone thickness around the implant at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration. The pink esthetic score (PES) was used to evaluate the esthetic outcomes after restoration. RESULTS: 18 patients were enrolled in this study. The survival rate of implants was 100%, and no complication was observed, except for 1 case of titanium mesh exposure which did not affect osteogenesis. In the second stage of surgery, the labial bone was completely reconstructed, and the top of the implant was covered with a small amount of new bone. The thickness of the labial bone was 3.01 mm (±0.23), 2.96 mm (±0.21), 2.93 mm (±0.19), and 2.92 mm (±0.16) at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration, respectively. The height of the marginal bone around implants was above the top of implant at the time of the second stage surgery and then reduced 0.72 mm (±0.07), 0.91 mm (±0.08), and 0.90 mm (±0.07) at the time point of 6 months, 1 year, and 2 years after restoration, respectively. The changes of bone thickness and height were statistically significant within one year, but stable after one year. The PES values showed the same tendency. CONCLUSIONS: With the limitation of the present prospective study, the combination of titanium mesh and CGF membrane could provide space maintenance for bone augmentation of alveolar bone defects and improve the bone regeneration in patients with severe labial bone defect when immediate implant of anterior maxillary.
Subject(s)
Bone Regeneration/drug effects , Intercellular Signaling Peptides and Proteins/administration & dosage , Maxilla/drug effects , Membranes/metabolism , Titanium/administration & dosage , Adult , Bone Transplantation/methods , Cone-Beam Computed Tomography/methods , Female , Humans , Male , Maxilla/surgery , Middle Aged , Prospective Studies , Prostheses and Implants , Plastic Surgery Procedures/methods , Surgical Mesh , Tooth Socket/drug effects , Tooth Socket/surgery , Young AdultABSTRACT
Despite the unique ability of lanthanide-doped upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light to high-energy UV-vis radiation, low quantum efficiency has rendered their application unpractical in biomedical fields. Here, we report anatase titania-coated plasmonic gold nanorods decorated with UCNPs (Au NR@aTiO2@UCNPs) for combinational photothermal and photodynamic therapy to treat cancer. Our novel architecture employs the incorporation of an anatase titanium dioxide (aTiO2) photosensitizer as a spacer and exploits the localized surface plasmon resonance (LSPR) properties of the Au core. The LSPR-derived near-field enhancement induces a threefold boost of upconversion emissions, which are re-absorbed by neighboring aTiO2 and Au nanocomponents. Photocatalytic experiments strongly infer that LSPR-induced hot electrons are injected into the conduction band of aTiO2, generating reactive oxygen species. As phototherapeutic agents, our hybrid nanostructures show remarkable in vitro anticancer effect under NIR light [28.0% cancer cell viability against Au NR@aTiO2 (77.3%) and UCNP@aTiO2 (98.8%)] ascribed to the efficient radical formation and LSPR-induced heat generation, with cancer cell death primarily following an apoptotic pathway. In vivo animal studies further confirm the tumor suppression ability of Au NR@aTiO2@UCNPs through combinatorial photothermal and photodynamic effect. Our hybrid nanomaterials emerge as excellent multifunctional phototherapy agents, providing a valuable addition to light-triggered cancer treatments in deep tissue.
Subject(s)
Antineoplastic Agents/pharmacology , Glioblastoma/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Glioblastoma/metabolism , Glioblastoma/pathology , Gold/administration & dosage , Gold/chemistry , Humans , Lanthanoid Series Elements/administration & dosage , Lanthanoid Series Elements/chemistry , Materials Testing , Mice , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Optical Imaging , Particle Size , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Titanium/administration & dosage , Titanium/chemistryABSTRACT
The economic approaches for manufacturing the nanoparticles with physical and chemical effects and limited resistance to antibiotics have been progressed recently due to the rise of microbial resistance to antibiotics. This research aimed to study the antimicrobial efficacy of silver nanoparticles Ag, ZnO, and Tio2 nanoparticles against Salmonella typhimurium and Brucella abortus and Candida albicans. Two isolates of Salmonella and two isolates of Brucella abortus were isolated from food spastically meat and blood specimens, respectively. Candida albicans were isolated from the patient's mouth with oral candidiasis (oral thrush) and confirmed diagnosis by API 20C test. The antimicrobial susceptibility of Salmonella typhimurium and B. abortus isolates were performed against nine different antibiotics. Silver nanoparticles consisting of AgNPs size (90) nm, ZnO NPs size (20, 50) nm as well as TiO2 NPs size (10, 50) nm, were used. UV-Visible spectrophotometer was used to characterize silver nanoparticles. The highest resistance of Candida albicans was seen for fluconazole, Clotrimazole and Itraconazole. The results of the Minimum Inhibitory Concentration (MIC) of nanoparticles against Salmonella typhimurium showed the average MIC of Tio2-10nm and Tio2-50nm were 5000 and 2500 µg\ml for S1 and S2 isolates, respectively. The isolated Brucella abortus (B1 and B2) showed sensitivity to NPs with different MIC. The average MIC for Ag-90nm was 5000 and 2500 µg/ml for B1 and B2 isolates, respectively. The findings suggest NP solution has fungicidal and bactericidal impacts on the tested microorganisms so they can be suitable for multiple applications of the biomedical field such as developing new antimicrobial agents.
Subject(s)
Bacteria/drug effects , Candida albicans/drug effects , Metal Nanoparticles/administration & dosage , Silver/pharmacology , Titanium/pharmacology , Zinc Oxide/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Bacteria/classification , Bacteria/growth & development , Brucella abortus/drug effects , Brucella abortus/growth & development , Candida albicans/growth & development , Clotrimazole/administration & dosage , Clotrimazole/chemistry , Clotrimazole/pharmacology , Drug Resistance, Fungal , Fluconazole/administration & dosage , Fluconazole/chemistry , Fluconazole/pharmacology , Humans , Itraconazole/administration & dosage , Itraconazole/chemistry , Itraconazole/pharmacology , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests/methods , Particle Size , Salmonella typhimurium/drug effects , Salmonella typhimurium/growth & development , Silver/administration & dosage , Silver/chemistry , Spectrophotometry/methods , Spectroscopy, Fourier Transform Infrared/methods , Titanium/administration & dosage , Titanium/chemistry , Zinc Oxide/administration & dosage , Zinc Oxide/chemistryABSTRACT
Alveolar macrophages are responsible for clearance of airborne dust and pathogens. How they recognize and phagocytose a variety of engineered nanomaterials (ENMs) with different properties is an important issue for safety assessment of ENMs. Surfactant-associated proteins, specifically existing in the pulmonary surfactant, are important opsonins for phagocytosis of airborne microorganisms. The purposes of the current study are to understand whether opsonization of ENMs by surfactant-associated proteins promotes phagocytosis of ENMs and cytokine production, and to determine whether a common pathway for phagocytosis of ENMs with different properties exists. For these purposes, four ENMs, MWCNT-7, TiO2, SiO2, and fullerene C60, with different shapes, sizes, chemical compositions, and surface reactivities, were chosen for this study. Short-term pulmonary exposure to MWCNT-7, TiO2, SiO2, and C60 induced inflammation in the rat lung, and most of the administered ENMs were phagocytosed by alveolar macrophages. The ENMs were phagocytosed by isolated primary alveolar macrophages (PAMs) in vitro, and phagocytosis was enhanced by rat bronchioalveolar lavage fluid (BALF), suggesting that proteins in the BALF were associated with phagocytosis. Analysis of proteins bound to the 4 ENMs by LC/MS indicated that surfactant-associated proteins A and D (SP-A, SP-D) were common binding proteins for all the 4 ENMs. Both BALF and SP-A, but not SP-D, enhanced TNF-α production by MWCNT-7 treated PAMs; BALF, SP-A, and SP-D increased IL-1ß production in TiO2 and SiO2 treated PAMs; and BALF, SP-A, and SP-D enhanced IL-6 production in C60 treated PAMs. Knockdown of CD14, a receptor for SP-A/D, significantly reduced phagocytosis of ENMs and SP-A-enhanced cytokine production by PAMs. These results indicate that SP-A/D can opsonize all the test ENMs and enhance phagocytosis of the ENMs by alveolar macrophages through CD14, suggesting that SP-A/D-CD14 is a common pathway mediating phagocytosis of ENMs. Cytokine production induced by ENMs, however, is dependent on the type of ENM that is phagocytosed. Our results demonstrate a dual role for surfactant proteins as opsonins for both microbes and for inhaled dusts and fibers, including ENMs, allowing macrophages to recognize and remove the vast majority of these particles, thereby, greatly lessening their toxicity in the lung.
Subject(s)
Cytokines/biosynthesis , Macrophages, Alveolar/immunology , Nanostructures/chemistry , Phagocytosis/immunology , Pulmonary Surfactant-Associated Proteins/immunology , Animals , Female , Fullerenes/administration & dosage , Fullerenes/chemistry , Inflammation/chemically induced , Inflammation/immunology , Nanostructures/administration & dosage , Nanotubes, Carbon/chemistry , Particle Size , Rats , Rats, Sprague-Dawley , Silicon Dioxide/administration & dosage , Silicon Dioxide/chemistry , Surface Properties , Titanium/administration & dosage , Titanium/chemistryABSTRACT
Adverse reactions to sunscreens are uncommon in relation to their widespread use [Loden et al. Br J Dermatol. 2011;165(2):255-62; Jansen et al. J Am Acad Dermatol. 2013;69(6):867 e861-814; quiz 881-862] and can be related to both active and inactive ingredients in sunscreen products [DiNardo et al. J Cosmet Dermatol. 2018;17(1):15-19; Barrientos et al. Contact Dermatitis. 2019;81(2):151-52]. Pathogenetically, the main cutaneous adverse reaction patterns to sunscreens can be divided into allergic and irritant contact dermatitis, phototoxic and photoallergic contact dermatitis, contact urticaria, and, in solitary cases, anaphylactic reactions [Lautenschlager et al. Lancet. 2007;370(9586):528-37]. A summary is provided in Table
Subject(s)
Dermatitis, Allergic Contact/etiology , Dermatitis, Irritant/etiology , Skin Neoplasms/prevention & control , Sunscreening Agents/adverse effects , Ultraviolet Rays/adverse effects , Dermatitis, Allergic Contact/pathology , Dermatitis, Allergic Contact/prevention & control , Dermatitis, Irritant/pathology , Dermatitis, Irritant/prevention & control , European Union , Humans , Pharmaceutical Vehicles/adverse effects , Pharmaceutical Vehicles/chemistry , Skin/drug effects , Skin/pathology , Skin/radiation effects , Skin Neoplasms/etiology , Sunscreening Agents/administration & dosage , Sunscreening Agents/chemistry , Titanium/administration & dosage , Titanium/adverse effects , Zinc Oxide/administration & dosage , Zinc Oxide/adverse effectsABSTRACT
High salt levels are one of the significant and major limiting factors on crop yield and productivity. Out of the available attempts made against high salt levels, engineered nanoparticles (NPs) have been widely employed and considered as effective strategies in this regard. Of these NPs, titanium dioxide nanoparticles (TiO2 NPs) and selenium functionalized using chitosan nanoparticles (Cs-Se NPs) were applied for a quite number of plants, but their potential roles for alleviating the adverse effects of salinity on stevia remains unclear. Stevia (Stevia rebaudiana Bertoni) is one of the reputed medicinal plants due to their diterpenoid steviol glycosides (stevioside and rebaudioside A). For this reason, the current study was designed to investigate the potential of TiO2 NPs (0, 100 and 200 mg L-1) and Cs-Se NPs (0, 10 and 20 mg L-1) to alleviate salt stress (0, 50 and 100 mM NaCl) in stevia. The findings of the study revealed that salinity decreased the growth and photosynthetic traits but resulted in substantial cell damage through increasing H2O2 and MDA content, as well as electrolyte leakage (EL). However, the application of TiO2 NPs (100 mg L-1) and Cs-Se NPs (20 mg L-1) increased the growth, photosynthetic performance and activity of antioxidant enzymes, and decreased the contents of H2O2, MDA and EL under the saline conditions. In addition to the enhanced growth and physiological performance of the plant, the essential oil content was also increased with the treatments of TiO2 (100 mg L-1) and Cs-Se NPs (20 mg L-1). In addition, the tested NPs treatments increased the concentration of stevioside (in the non-saline condition and under salinity stress) and rebaudioside A (under the salinity conditions) in stevia plants. Overall, the current findings suggest that especially 100 mg L-1 TiO2 NPs and 20 mg L-1 Cs-Se could be considered as promising agents in combating high levels of salinity in the case of stevia.
Subject(s)
Chitosan/chemistry , Nanoparticles/administration & dosage , Plant Leaves/growth & development , Salt Stress/drug effects , Selenium/administration & dosage , Stevia/growth & development , Titanium/administration & dosage , Nanoparticles/chemistry , Photosynthesis , Selenium/chemistry , Stevia/drug effects , Titanium/chemistryABSTRACT
BACKGROUND: Nanotechnologies provide new opportunities for improving the safety, quality, shelf life, flavor and appearance of foods. The most common nanoparticles (NPs) in human diet are silver metal, mainly present in food packaging and appliances, and silicon and titanium dioxides used as additives. The rapid development and commercialization of consumer products containing these engineered NPs is, however, not well supported by appropriate toxicological studies and risk assessment. Local and systemic toxicity and/or disruption of the gut microbiota (GM) have already been observed after oral administration of NPs in experimental animals, but results are not consistent and doses used were often much higher than the estimated human intakes. In view of the strong evidence linking alterations of the GM to cardiometabolic (CM) diseases, we hypothesized that dietary NPs might disturb this GM-CM axis. MATERIALS AND METHODS: We exposed male C57BL/6JRj mice (n = 13 per dose group) to dietary NPs mixed in food pellets at doses relevant for human exposure: Ag (0, 4, 40 or 400 µg/kg pellet), SiO2 (0, 0.8, 8 and 80 mg/kg pellet) or TiO2 (0, 0.4, 4 or 40 mg/kg pellet). After 24 weeks of exposure, we assessed effects on the GM and CM health (n = 8 per dose group). The reversibility of the effects was examined after 8 additional weeks without NPs exposure (recovery period, n ≤ 5 per dose group). RESULTS: No overt toxicity was recorded. The GM ß-diversity was dose-dependently disrupted by the three NPs, and the bacterial short chain fatty acids (SCFAs) were dose-dependently reduced after the administration of SiO2 and TiO2 NPs. These effects disappeared completely or partly after the recovery period, strengthening the association with dietary NPs. We did not observe atheromatous disease or glucose intolerance after NP exposure. Instead, dose-dependent decreases in the expression of IL-6 in the liver, circulating triglycerides (TG) and urea nitrogen (BUN) were recorded after administration of the NPs. CONCLUSION: We found that long-term oral exposure to dietary NPs at doses relevant for estimated human intakes disrupts the GM composition and function. These modifications did not appear associated with atheromatous or deleterious metabolic outcomes.
Subject(s)
Dietary Exposure/adverse effects , Gastrointestinal Microbiome/drug effects , Metal Nanoparticles/chemistry , Administration, Oral , Animals , Bacteria/drug effects , Bacteria/metabolism , Fatty Acids, Volatile/metabolism , Interleukin-6/metabolism , Male , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/toxicity , Mice, Inbred C57BL , Silicon Dioxide/administration & dosage , Silicon Dioxide/pharmacology , Silicon Dioxide/toxicity , Silver/administration & dosage , Silver/pharmacology , Silver/toxicity , Titanium/administration & dosage , Titanium/pharmacology , Titanium/toxicity , Triglycerides/metabolismABSTRACT
Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.
Subject(s)
Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Peri-Implantitis/prevention & control , Peri-Implantitis/therapy , Titanium/pharmacology , Amines/administration & dosage , Amines/chemistry , Amines/pharmacology , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Biofilms/growth & development , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Dental Implants , Drug Stability , Humans , In Vitro Techniques , Male , Materials Testing , Osseointegration/drug effects , Peri-Implantitis/microbiology , Porosity , Rabbits , Surface Properties , Titanium/administration & dosage , Titanium/chemistryABSTRACT
Nonfibrous potassium octatitanate particles are commercially utilized in applications such as brake pads or brake linings. The aim of this study was to assess lung toxicity in rats exposed to Terracess JS particle-types, one form of nonfibrous octatitanate particulates, and compare the effects to vehicle controls and to Min-U-Sil α-quartz particles as a positive benchmark control particle. Groups of male rats were intratracheally instilled with doses of either 1 or 5 mg/kg of Terracess JS particles or α-quartz particles in phosphate-buffered saline. Phosphate-buffered saline (PBS) solution instilled rats served as vehicle controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory biomarkers at post-instillation time points of 1 week, 1 month, and 3 months. In addition, lung tissue morphologies from PBS or 5 mg/kg particle-exposed (Terracess JS or α-quartz) rats were evaluated at postexposure time points of 1 month and 3 months. The BAL fluid results demonstrated that pulmonary instillation exposures in rats to quartz particles produced sustained pulmonary inflammation and significant cytotoxic effects measured at 1 week, 1 month and 3 months postexposure. In contrast, exposures to Terracess JS particle-types produced no significant lung inflammatory or cell injury effects when compared to PBS vehicle control exposed rats. With regard to histopathology of lung tissue, pulmonary exposures to quartz particles in rats produced a progressive, dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation, as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis at the 3-month postexposure time period. In contrast, histopathological analyses of lung tissues revealed that pulmonary exposures to Terracess JS particulates resulted in no significant adverse effects when compared to PBS-exposed controls, as evidenced by the normal lung architecture observed in the exposed animals at post-instillation exposure time periods ranging from 1 month to 3 months. The results described herein demonstrate the benign nature of the pulmonary instillation response in rats following particle exposures to 1 or 5 mg/kg (approximately 1.25 mg) of Terracess JS particle-types in these pulmonary bioassay studies, using appropriate benchmark control particles for comparative evaluations. Thus, based on these results, it is concluded that inhaled Terracess JS particles are expected to have a low-risk potential for producing adverse pulmonary health effects in exposed workers.
Subject(s)
Particulate Matter/toxicity , Titanium/toxicity , Administration, Inhalation , Animals , Automobiles , Biological Assay , Bronchoalveolar Lavage Fluid/cytology , Inhalation Exposure , Lung/drug effects , Lung/pathology , Male , Organ Size/drug effects , Particulate Matter/administration & dosage , Pneumonia/chemically induced , Pneumonia/pathology , Rats , Titanium/administration & dosageABSTRACT
Background Despite recent progressions in the treatment of melanoma, the response to conventional therapies and the long-term survival in melanoma patients still remain poor. Recently, the use of nanoparticles (NPs) has been highlighted for promoting the chemotherapeutic effects of cytotoxic drugs in melanoma. The aim of this study is to mechanistically evaluate the potential of titanium dioxide (TiO2) nanoparticles (NPs) for enhancing chemotherapy effects in in vitro and in vivo models of murine melanoma. Methods The F10 melanoma cells were exposed to different concentrations of TiO2 NPs and/or cisplatin, then cell growth, cell viability, and cell death were evaluated. In parallel, C57BL/6 syngeneic melanoma mice were treated by TiO2 NPs and/or cisplatin, and then drug responses, tumor size and mices organs were studied pathologically. Autophagy was examined by evaluating the formation of autophagosomes and gene expression levels of autophagy markers (ATG5 and ATG6) by fluorescent microscopy and qPCR, respectively. Results Nontoxic concentrations of TiO2 NPs (50 µg/ml) promote anti-proliferative and cytotoxic effects of cisplatin in F10 melanoma cells, which is mediated through the induction of autophagy and necrotic cell death. Whereas TiO2 NPs have no cytotoxic or metastatic effects in melanoma mice, its combination with cisplatin enhances drug responses (up to 50%), leading to higher inhibition of tumor growth compared with each monotherapy. Conclusion The combination of TiO2 NP with cisplatin enhances chemotherapy response in both in vitro and in vivo melanoma models. In addition, autophagy plays an essential role during sensitizing melanoma cells to chemotherapy (AU)
Subject(s)
Animals , Male , Mice , Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Melanoma, Experimental/drug therapy , Nanoparticles/administration & dosage , Titanium/administration & dosage , Antineoplastic Combined Chemotherapy Protocols , Disease Models, Animal , Melanoma, Experimental/pathology , Mice, Inbred C57BL , Cell Proliferation , Cell SurvivalABSTRACT
Macrophages are key innate immune cells that mediate implant acceptance or rejection. Titanium implants degrade over time inside the body, which results in the release of implant wear-off particles. Titanium nanoparticles (TiNPs) favor pro-inflammatory macrophage polarization (M1) and lower tolerogenic activation (M2). GDF-15 regulates immune tolerance and fibrosis and is endocytosed by stabilin-1. How TiNPs affect the healing activities of macrophages and their release of circulating cytokines is an open question in regenerative medicine. In this study for the first time, we identified the transcriptional program induced and suppressed by TiNPs in human pro-inflammatory and healing macrophages. Microarray analysis revealed that TiNPs altered the expression of 5098 genes in M1 (IFN-γ-stimulated) and 4380 genes in M2 (IL-4-stimulated) macrophages. 1980 genes were differentially regulated in both M1 and M2. Affymetrix analysis, confirmed by RT-PCR, demonstrated that TiNPs upregulate expression of GDF-15 and suppress stabilin-1, scavenger receptor of GDF-15. TiNPs also significantly stimulated GDF-15 protein secretion in inflammatory and healing macrophages. Flow cytometry demonstrated, that scavenging activity of stabilin-1 was significantly suppressed by TiNPs. Confocal microscopy analysis showed that TiNPs impair internalization of stabilin-1 ligand acLDL and its transport to the endocytic pathway. Our data demonstrate that TiNPs have a dual effect on the GDF-15/stabilin-1 interaction in macrophage system, by increasing the production of GDF-15 and suppressing stabilin-1-mediated clearance function. In summary, this process can result in a significant increase of GDF-15 in the extracellular space and in circulation leading to unbalanced pro-fibrotic reactions and implant complications.
Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Growth Differentiation Factor 15/metabolism , Macrophages/drug effects , Nanoparticles/administration & dosage , Receptors, Lymphocyte Homing/metabolism , Titanium/administration & dosage , Cell Adhesion Molecules, Neuronal/genetics , Cells, Cultured , Endocytosis , Gene Expression/drug effects , Growth Differentiation Factor 15/genetics , Humans , Macrophages/metabolism , Prostheses and Implants , Receptors, Lymphocyte Homing/geneticsABSTRACT
Infection is the second leading cause of failure of orthopedic implants following incomplete osseointegration. Materials that increase the antimicrobial properties of surfaces while maintaining the ability for bone cells to attach and proliferate could reduce the failure rates of orthopedic implants. In this study, titania nanotubes (Nts) were modified with chitosan/heparin polyelectrolyte multilayers (PEMs) for gentamicin delivery. The antimicrobial activity of the surfaces was tested by coculturing bacteria with mammalian cells. Over 60% of gentamicin remained on the surface after an initial burst release on the first day. Antimicrobial activity of these surfaces was determined by exposure to Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) for up to 24 h. Gentamicin surfaces had less live E. coli and S. aureus by 6 h and less E. coli by 24 h compared to Nt surfaces. S. aureus and human adipose-derived stem cells (hADSCs) were cocultured on surfaces for up to 7 days to characterize the so-called "race to the surface" between bacteria and mammalian cells, which is hypothesized to ultimately determine the outcome of orthopedic implants. By day 7, there was no significant difference in bacteria between surfaces with gentamicin adsorbed on the surface and surfaces with gentamicin in solution. However, gentamicin delivered in solution is toxic to hADSCs. Alternatively, gentamicin presented from PEMs enhances the antimicrobial properties of the surfaces without inhibiting hADSC attachment and cell growth. Delivering gentamicin from the surfaces is therefore superior to delivering gentamicin in solution and represents a strategy that could improve the antimicrobial activity of orthopedic implants and reduce risk of failure due to infection, without reducing mammalian cell attachment.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Escherichia coli/drug effects , Gentamicins/administration & dosage , Mesenchymal Stem Cells/drug effects , Nanotubes , Staphylococcus aureus/drug effects , Titanium/administration & dosage , Anti-Bacterial Agents/chemistry , Cells, Cultured , Coculture Techniques , Drug Liberation , Gentamicins/chemistry , Humans , Nanotubes/chemistry , Titanium/chemistryABSTRACT
BACKGROUND: Despite recent progressions in the treatment of melanoma, the response to conventional therapies and the long-term survival in melanoma patients still remain poor. Recently, the use of nanoparticles (NPs) has been highlighted for promoting the chemotherapeutic effects of cytotoxic drugs in melanoma. The aim of this study is to mechanistically evaluate the potential of titanium dioxide (TiO2) nanoparticles (NPs) for enhancing chemotherapy effects in in vitro and in vivo models of murine melanoma. METHODS: The F10 melanoma cells were exposed to different concentrations of TiO2 NPs and/or cisplatin, then cell growth, cell viability, and cell death were evaluated. In parallel, C57BL/6 syngeneic melanoma mice were treated by TiO2 NPs and/or cisplatin, and then drug responses, tumor size and mice's organs were studied pathologically. Autophagy was examined by evaluating the formation of autophagosomes and gene expression levels of autophagy markers (ATG5 and ATG6) by fluorescent microscopy and qPCR, respectively. RESULTS: Nontoxic concentrations of TiO2 NPs (50 µg/ml) promote anti-proliferative and cytotoxic effects of cisplatin in F10 melanoma cells, which is mediated through the induction of autophagy and necrotic cell death. Whereas TiO2 NPs have no cytotoxic or metastatic effects in melanoma mice, its combination with cisplatin enhances drug responses (up to 50%), leading to higher inhibition of tumor growth compared with each monotherapy. CONCLUSION: The combination of TiO2 NP with cisplatin enhances chemotherapy response in both in vitro and in vivo melanoma models. In addition, autophagy plays an essential role during sensitizing melanoma cells to chemotherapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Autophagy/drug effects , Cisplatin/therapeutic use , Melanoma, Experimental/drug therapy , Nanoparticles/therapeutic use , Titanium/therapeutic use , Animals , Antineoplastic Agents/administration & dosage , Autophagosomes , Autophagy/genetics , Autophagy-Related Protein 5/genetics , Beclin-1/genetics , Cell Death/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cisplatin/administration & dosage , Drug Combinations , Drug Synergism , Kidney/drug effects , Liver/drug effects , Male , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Necroptosis/drug effects , Particle Size , Random Allocation , Spleen/drug effects , Titanium/administration & dosage , Tumor Burden/drug effectsSubject(s)
Skin Care/economics , Skin Neoplasms/prevention & control , Sunscreening Agents/chemistry , Titanium/economics , Zinc Oxide/economics , Cost-Benefit Analysis , Humans , Patient Compliance , Skin/drug effects , Skin/radiation effects , Skin Care/methods , Skin Neoplasms/etiology , Sunscreening Agents/administration & dosage , Sunscreening Agents/economics , Titanium/administration & dosage , Titanium/chemistry , Ultraviolet Rays/adverse effects , Zinc Oxide/administration & dosage , Zinc Oxide/chemistryABSTRACT
OBJECTIVE: Treatment of lumbosacral tuberculosis is still controversial. In our study, we assessed the efficacy and feasibility of single-stage posterior debridement, interbody fusion using a structural autograft combined with a titanium mesh cage, and posterior instrumentation for the treatment of lumbosacral tuberculosis with significant vertebral body loss. METHODS: From May 2011 to June 2018, 15 patients with lumbosacral tuberculosis with significant vertebral body loss had undergone single-stage posterior debridement, interbody fusion using a structural autograft combined with a titanium mesh cage, and posterior instrumentation. The pre- and postoperative lumbosacral angle, visual analog scale score, erythrocyte sedimentation rate, C-reactive protein, and neurological status were assessed. RESULTS: Surgery was successful for all patients, and no patient experienced tuberculosis recurrence during an average follow-up period of 27.3 months (range, 12-60 months). After surgery, the erythrocyte sedimentation rate and C-reactive protein for all patients had returned to normal within 3 months. At the final follow-up examination, the neurological status had improved in all patients who had had neurological deficits preoperatively. The mean preoperative lumbosacral angle was 12.6° (range, 6.7°-17.9°), and had increased to 27.7° (range, 24.3°-34.6°) after surgery. The average lumbosacral angle was 26.4° (range, 22.1°-32.3°), with an average loss of 1.4° (range, 0.6°-2.3°) at the final follow-up visit. CONCLUSIONS: The combination of single-stage posterior debridement, interbody fusion using structural autografts with a titanium mesh cage, and posterior instrumentation is an effective and safe option for the treatment of lumbosacral tuberculosis with significant vertebral body loss.
Subject(s)
Autografts/transplantation , Lumbar Vertebrae/surgery , Sacrum/surgery , Surgical Mesh , Tuberculosis, Spinal/surgery , Vertebral Body/surgery , Adolescent , Adult , Aged , Autografts/diagnostic imaging , Debridement/methods , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Prostheses and Implants , Retrospective Studies , Sacrum/diagnostic imaging , Spinal Fusion/instrumentation , Spinal Fusion/methods , Titanium/administration & dosage , Treatment Outcome , Tuberculosis, Spinal/diagnostic imaging , Vertebral Body/diagnostic imaging , Young AdultABSTRACT
The application of metal nanoparticles in modern society is growing, but there is insufficient data concerning their influence on reproductive processes and comparison of their biological activity. The present experiments aimed to compare the effects of silver and titanium dioxide nanoparticles (AgNPs and TiO2NPs) on ovarian granulosa cell functions. AgNPs and TiO2NPs were added to culture of porcine granulosa cells at doses 0, 0.01, 0.1, 1 or 10 µg/mL. The mRNAs for proliferating cell nuclear antigen (PCNA), cyclin B1, bax and caspase 3 were quantified by RT-PCR; release of progesterone was analyzed by ELISA. It was shown that both AgNPs and TiO2NPs significantly reduced all the measured parameters. ED50 of the inhibitory influence of AgNPs on the main ovarian cell parameters was higher than ED50 of TiO2NPs. The ability of AgNPs and TiO2NPs to suppress ovarian granulosa cell functions should be taken into account by their application.
Subject(s)
Granulosa Cells/drug effects , Metal Nanoparticles/toxicity , Silver Compounds/toxicity , Titanium/toxicity , Animals , Caspases/genetics , Caspases/metabolism , Cells, Cultured , Cyclin B1/genetics , Cyclin B1/metabolism , Dose-Response Relationship, Drug , Female , Gene Expression Regulation/drug effects , Metal Nanoparticles/administration & dosage , Progesterone/metabolism , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Silver Compounds/administration & dosage , Swine , Titanium/administration & dosage , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
Due to the physicochemical properties of nanoparticles, the use of nanomaterials increases over time in industrial and medical processes. We herein report the negative impact of nanoparticles, using solid growth conditions mimicking a biofilm, on the ability of Bacillus subtilis to fight against a stress. Bacteria have been exposed to sublethal doses of nanoparticles corresponding to conditions that bacteria may meet in their natural biotopes, the upper layer of soil or the gut microbiome. The analysis of the proteomic data obtained by shotgun mass spectrometry have shown that several metabolic pathways are affected in response to nanoparticles, n-ZnO or n-TiO2, or zinc salt: the methyglyoxal and thiol metabolisms, the oxidative stress and the stringent responses. Nanoparticles being embedded in the agar medium, these impacts are the consequence of a physiological adaptation rather than a physical cell injury. Overall, these results show that nanoparticles, by altering bacterial physiology and especially the ability to resist to a stress, may have profound influences on a "good bacteria", Bacillus subtilis, in its natural biotope and moreover, on the global equilibrium of this biotope.