ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ËO2-, H2O2, and ËOH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Nanocomposites , Phosphorus , Photochemotherapy , Photothermal Therapy , Titanium , Titanium/chemistry , Titanium/pharmacology , Phosphorus/chemistry , Humans , Animals , Nanocomposites/chemistry , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Mice , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/therapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Survival/drug effects , Cell Proliferation/drug effects , Mice, Nude , Mice, Inbred BALB C , Drug Screening Assays, Antitumor , Particle Size , Cell Line, TumorABSTRACT
Photothermal therapy (PTT) has attracted much attention due to its less invasive, controllable and highly effective nature. However, PTT also suffers from intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by a variety of proteins, among which heat shock protein (HSP) triggers thermotolerance and protects tumor cells from hyperthermia-induced apoptosis. Confronted by this challenge, we propose and validate here a novel MXene-based HSP-inhibited mild photothermal platform, which significantly enhances the sensitivity of tumor cells to heat-induced stress and thus improves the PPT efficacy. The Ti3C2@Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti3C2 nanosheets in combination with quercetin (Qu) as an inhibitor of HSP70. Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of heat shock protein 70 (HSP70) in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. The nanostructure, photothermal properties, pH-responsive controlled release, synergistic photothermal ablation of tumor cells in vitro and in vivo, and hyperthermia effect on subcellular structures of the Ti3C2@Qu nanocomposites were systematically investigated.
Subject(s)
Hyperthermia, Induced , Nanocomposites , Nanoparticles , Neoplasms , Nitrites , Transition Elements , Humans , Delayed-Action Preparations , Titanium/pharmacology , Phototherapy , Neoplasms/therapy , Cell Line, Tumor , Nanoparticles/chemistryABSTRACT
Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.
Subject(s)
Hyperthermia, Induced , Neoplasms , Nitrites , Transition Elements , Humans , Glucose Oxidase , Hydrogen Peroxide , Titanium/pharmacology , Hyperthermia , Neoplasms/therapy , Glucose , Hypoxia , Tumor Microenvironment , Cell Line, TumorABSTRACT
The present study describes a method for the preparation of green titanium dioxide (TiO2) nanoparticles from the peel of Solanum tuberosum, commonly known as potato, and the potato peel being a kitchen waste. The green synthesized TiO2 (G- TiO2) nanoparticles were characterized using UV-visible spectroscopy, dynamic light scattering, scanning electron microscopy, TEM, XRD, and FTIR spectroscopy. The photocatalytic activity of the G- TiO2 nanoparticles was also shown using the dye bromophenol blue. To explore the biocompatibility of the G- TiO2, the cell viability in normal as well as cancer cells was assessed. Further, the in vivo toxicity of the G- TiO2 nanoparticles was assessed using zebrafish embryos. The novelty of the present invention is to utilize kitchen waste for a useful purpose for the synthesis of titanium dioxide nanoparticles which is known to have UV light scavenging properties. Moreover, the potato peel is a natural antioxidant and possesses a skin-lightening effect. A combination of the potato peel extract and titanium dioxide prepared using the extract will have a combinatorial effect for protecting UV light exposure to the skin and lightening the skin colour.
Subject(s)
Nanoparticles , Solanum tuberosum , Animals , Zebrafish , Nanoparticles/chemistry , Titanium/pharmacology , Titanium/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , CatalysisABSTRACT
The repair and reconstruction of large bone defects after bone tumor resection is still a great clinical challenge. At present, orthopedic implant reconstruction is the mainstream treatment for repairing bone defects. However, according to clinical feedback, local tumor recurrence and nonunion of bone graft are common reasons leading to the failure of bone defect repair and reconstruction after bone tumor resection, which seriously threaten the physical and mental health of patients. On this basis, here the self-developed low modulus Ti-12Mo-10Zr alloy (TMZ) was chosen as substrate material. To improve its biological activity and osteointegration, calcium, oxygen, and phosphorus co-doped microporous coating was prepared on TMZ alloy by microarc oxidation (MAO). Then, black phosphorus (BP) nanosheets were incorporated onto MAO treated TMZ alloy to obtain multifunctional composites. The obtained BP-MAO-TMZ implant exhibited excellent photothermal effects and effective ablation of osteosarcoma cancer cells under the irradiation of 808 nm near infrared laser, while no photothermal or therapeutic effects were observed for TMZ alloy. Meanwhile, the structure/component bionic coating obtained after MAO treatment as well as the P-driven in situ biomineralization performance after incorporation of BP nanosheets endowed BP-MAO-TMZ implant with synergistic promoting effect on MC3T3-E1 osteoblasts' activity, proliferation and differentiation ability. This study is expected to provide effective clinical solutions for problems of difficult bone regeneration and tumor recurrence after tumor resection in patients with bone tumors and to solve a series of medical problems such as poor prognosis and poor postoperative quality of patients life with malignant bone tumors.
Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Phosphorus , Titanium/pharmacology , Neoplasm Recurrence, Local , Osteosarcoma/drug therapy , Bone Neoplasms/drug therapy , Combined Modality Therapy , Alloys/pharmacologyABSTRACT
The utilization of ultrasound (US) to activate sonosensitizers for sonodynamic therapy (SDT) has faced challenges such as low activation efficiency and limited therapeutic outcomes, which have hampered its clinical applications. In this study, a nanohybrid of titanium dioxide-gold-polyethylene glycol-curcumin (TiO2-Au-PEG-Cur NH), as a novel US sensitizer, was synthesized, characterized, and applied for SDT of HeLa cancer cells in 2D monolayer model, and also a 3D spheroid model to bridge the gap between 2D cell culture and in vivo future studies. TiO2-Au-PEG-Cur NH contained TiO2 nanoparticles of 36 ± 11 nm in diameter, PEG-curcumin as a filler, and gold nanoparticles of 21 ± 7 nm in diameter with a high purity and a 35:17 of Ti:Au ratio (W/W), and it had a band gap of 2.4 eV, a zeta potential of -23 ± 7 mV, high stability upon US radiation cycles as well as one year storage. SDT of HeLa cells using TiO2-Au-PEG-Cur NH was investigated in the courses of cytotoxicity assessment in vitro, reactive oxygen species (ROS) generation capability, colony formation, cell migration, and the way to form spheroid. IC50 values of 122 and 38 µg mL-1 were obtained for TiO2-Au-PEG-Cur NH without and with US radiation, respectively. TiO2-Au-PEG-Cur NH not only exhibited an inherent capacity to generate ROS, but also represented an excellent therapeutic performance on the cancer cells through ROS generation and enhanced inhibitory effects on cell migration and spheroid formation.
Subject(s)
Curcumin , Metal Nanoparticles , Nanoparticles , Neoplasms , Humans , Curcumin/pharmacology , HeLa Cells , Polyethylene Glycols/pharmacology , Gold/pharmacology , Reactive Oxygen Species/metabolism , Titanium/pharmacology , Cell Line, TumorABSTRACT
Bone metastases severely threaten the lives of patients. Although surgical treatment combined with adjuvant chemotherapy significantly improves the survival rate of patients, tumor recurrence, or metastasis after surgical resection and bone defects caused by surgical treatment remain major challenges for clinicians. Given the abovementioned clinical requirements, barium titanate-containing iron-coated porous titanium alloy scaffolds have been proposed to promote bone defect repair and inhibit tumor recurrence. Fortunately, in vitro and in vivo experimental research confirms that barium titanate containing iron-coated porous titanium alloy scaffolds promote osteogenesis and bone reconstruction in defect repair via mechanoelectric conversion and inhibit tumor recurrence via photothermal effects. Furthermore, the underlying and intricate mechanisms of bone defect repair and tumor recurrence prevention of barium titanate-containing iron-coated porous titanium alloy scaffolds are explored. A win-win strategy for mechanoelectrical conversion and photothermal functionalization provides promising insights into bone reconstruction of tumor-resected defects.
Subject(s)
Tissue Scaffolds , Titanium , Humans , Titanium/pharmacology , Porosity , Barium , Neoplasm Recurrence, Local , Osteogenesis , Alloys , IronABSTRACT
The abuse of antibiotics leads to an increasing emergence of drug-resistant bacteria, which not only causes a waste of medical resources but also seriously endangers people's health and life safety. Therefore, it is highly desirable to develop an efficient antibacterial strategy to reduce the reliance on traditional antibiotics. Antibacterial photodynamic therapy (aPDT) is regarded as an intriguing antimicrobial method that is less likely to generate drug resistance, but its efficiency still needs to be further improved. Herein, a robust titanium-based metal-organic framework ACM-1 was adopted to support Ag nanoparticles (NPs) to obtain Ag NPs@ACM-1 for boosting antibacterial efficiency via synergistic chemical-photodynamic therapy. Apart from the intrinsic antibacterial nature, Ag NPs largely boost ROS production and thus improve aPDT efficacy. As a consequence, Ag NPs@ACM-1 shows excellent antibacterial activity under visible light illumination, and its minimum bactericidal concentrations (MBCs) against E. coli, S. aureus, and MRSA are as low as 39.1, 39.1, and 62.5 µg mL-1, respectively. Moreover, to expand the practicability of Ag NPs@ACM-1, two (a dense and a loose) Ag NPs@ACM-1 films were readily fabricated by simply dispersing Ag NPs@ACM-1 into heated aqueous solutions of edible agar and sequentially cooling through heating or freeze-drying, respectively. Notably, these two films are mechanically flexible and exhibit excellent antibacterial activities, and their antimicrobial performances can be well retained in their recyclable and remade films. As agar is nontoxic, degradable, inexpensive, and ecosustainable, the dense and loose Ag NPs@ACM-1 films are potent to serve as recyclable and degradable antibacterial plastics and antibacterial dressings, respectively.
Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Metal-Organic Frameworks , Photochemotherapy , Humans , Silver/pharmacology , Titanium/pharmacology , Metal-Organic Frameworks/pharmacology , Staphylococcus aureus , Escherichia coli , Agar , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity TestsABSTRACT
Objective: To review antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants, so as to provide reference for subsequent research. Methods: The related research literature on antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants in recent years was reviewed, and the research progress was summarized based on different kinds of antibacterial substances and osteogenic active substances. Results: At present, the antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants includes: â Combined coating strategy of antibiotics and osteogenic active substances. It is characterized in that antibiotics can be directly released around titanium-based implants, which can improve the bioavailability of drugs and reduce systemic toxicity. â¡ Combined coating strategy of antimicrobial peptides and osteogenic active substances. The antibacterial peptides have a wide antibacterial spectrum, and bacteria are not easy to produce drug resistance to them. ⢠Combined coating strategy of inorganic antibacterial agent and osteogenic active substances. Metal ions or metal nanoparticles antibacterial agents have broad-spectrum antibacterial properties and various antibacterial mechanisms, but their high-dose application usually has cytotoxicity, so they are often combined with substances that osteogenic activity to reduce or eliminate cytotoxicity. In addition, inorganic coatings such as silicon nitride, calcium silicate, and graphene also have good antibacterial and osteogenic properties. ⣠Combined coating strategy of metal organic frameworks/osteogenic active substances. The high specific surface area and porosity of metal organic frameworks can effectively package and transport antibacterial substances and bioactive molecules. ⤠Combined coating strategy of organic substances/osteogenic active substancecs. Quaternary ammonium compounds, polyethylene glycol, N-haloamine, and other organic compounds have good antibacterial properties, and are often combined with hydroxyapatite and other substances that osteogenic activity. Conclusion: The factors that affect the antibacterial and osteogenesis properties of titanium-based implants mainly include the structure and types of antibacterial substances, the structure and types of osteogenesis substances, and the coating process. At present, there is a lack of clinical verification of various strategies for antibacterial/osteogenesis dual-functional surface modification of titanium-based implants. The optimal combination, ratio, dose-effect mechanism, and corresponding coating preparation process of antibacterial substances and bone-active substances are needed to be constantly studied and improved.
Subject(s)
Anti-Bacterial Agents , Metal-Organic Frameworks , Titanium , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/chemistry , Metal-Organic Frameworks/pharmacology , Osteogenesis , Surface Properties , Titanium/chemistry , Titanium/pharmacology , Prostheses and ImplantsABSTRACT
Cervical cancer is the most common and deadly female cancer on the worldwide scale. Considering that the conventional surgery treatment and chemotherapy would cause certain side effects, photothermal therapy (PTT) possesses desired therapeutic efficiency and insignificant side effects against cervical cancer. However, the lack of efficient and safe photothermal agents that operate in the second near-infrared (NIR-II) window is a main obstacle hindering the clinical transformation of PTT. Titanium dioxide (TiO2)-based nanomaterials are commonly applied in the biomedicine field, but the weak absorption and low photothermal conversion efficiency (PCE) of TiO2 in the NIR region limit their applications in PTT. Herein, we report the oxygen vacancy engineering that is a robust strategy to regulate the electronic structures of TiO2 for photothermal conversion properties optimizing. The obtained oxygen vacancy-doped TiO2-x nanosheets exhibit strong NIR-II absorption and high PCE owing to their decreased bandgap. Specifically, the PCE of TiO2-x nanosheets is determined to be 69.5 % in the efficient NIR-II window, which is much higher than that of widely reported PTT agents. Complete tumor recession without recurrence or pulmonary metastasis is realized by enhanced NIR-II PTT via TiO2-x nanosheets at an ultralow and safe laser exposure (0.6 W/cm2). Our findings suggest that oxygen vacancy engineering of nanomaterials could regulate their photothermal conversion performances, promoting the further application of TiO2-based nanomaterials in the biomedical.
Subject(s)
Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/therapy , Photothermal Therapy , Oxygen , Neoplasms/drug therapy , Titanium/pharmacology , Titanium/chemistry , PhototherapyABSTRACT
Rapid and sustainable green technology was implemented in the current study to fabricated Ti nanoparticles. The vegetable ginger with the scientific name Zingiber officinale was employed as a biological source in the fabrication process of nanoparticles. The optical, structural, morphological, and particle size of the fabricated Ti nanoparticles were characterized with the help of UV-visible absorption spectrum, FTIR (Fourier Transform Infrared) spectrum, SEM (Scanning Electron Microscope) analysis, DLS (Dynamic Light Scattering) technique and XRD (X-ray powder diffraction) crystallography technique. The presence of spherical-shaped Ti nanoparticles with an average particle size of 93 nm was confirmed based on these characterization techniques. The anti-cancer properties of the Z. officinale mediated Ti nanoparticles were analyzed through MTT assay against cell lines MCF-7 (Human breast adenocarcinoma cell line) and concentration-dependent anti-cancer properties were observed. The anti-inflammatory capacity of the Z. officinale mediated Ti nanoparticles were examined through protein denaturation and nitric oxide scavenging assay. The antioxidant capacity of the Z. officinale mediated Ti nanoparticles were examined through DPPH assay, hydrogen peroxide radical scavenging assay, hydroxyl radical scavenging assay, and FRAP (Ferric Reducing Antioxidant Power) analysis. The fabricated Ti nanoparticles exhibited anti-inflammatory and antioxidant capacity in a concentration-dependent pattern.
Subject(s)
Metal Nanoparticles , Zingiber officinale , Humans , Antioxidants/pharmacology , Zingiber officinale/chemistry , Anti-Bacterial Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Metal Nanoparticles/chemistry , Titanium/pharmacology , Spectroscopy, Fourier Transform InfraredABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) has strong resistance to antibiotic therapy. In this regard, developing antibiotic-free antibacterial agents is of great significance to treat MRSA infections. Herein, we loaded Ti3C2Tx MXene nanomaterial in the non-crosslinked chitosan (CS) hydrogel. The obtained MX-CS hydrogel is expected to not only adsorb MRSA cells via CS-MRSA interactions, but also gather the MXene-induced photothermal hyperthermia, achieving the efficient and intensive anti-MRSA photothermal therapy. As a result, under NIR irradiation (808 nm, 1.6 W/cm2, 5 min), MX-CS showed a greater photothermal effect than MXene alone did (30 µg/mL, 49.9 °C for MX-CS and 46.5 °C for MXene). Importantly, MRSA cells were rapidly adsorbed on MX-CS hydrogel (containing 30 µg/mL MXene) and completely inhibited (99.18 %) under NIR irradiation for 5 min. In contrast, MXene (30 µg/mL) and CS hydrogel alone only inhibited 64.52 % and 23.72 % MRSA, respectively, significantly lower than the inhibition caused by MX-CS (P < 0.001). Interestingly, when the hyperthermia was depleted by a 37 °C water bath, the bacterial inhibition rate of MX-CS significantly decreased to 24.65 %. In conclusion, MX-CS hydrogel has a remarkable synergistic anti-MRSA activity by gathering MRSA cells and MXene-induced hyperthermia, and may have great potentials in treating MRSA-infected diseases.
Subject(s)
Chitosan , Methicillin-Resistant Staphylococcus aureus , Chitosan/pharmacology , Hydrogels/pharmacology , Titanium/pharmacology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacologyABSTRACT
Integrin-mediated osteoblast adhesion to adsorbed extracellular ligands on orthopedic implants is crucial for the subsequent osteoblast behaviors and ultimate osseointegration. Considerable research efforts have focused on the development of implant surfaces that promote the adsorption of extracellular ligands, but ignored the fact that integrin binding to ligands requires divalent cations (such as Mn2+). Here, three kinds of Mn-doped nanowire-structured TiO2 coatings with 1.9, 3.9, and 8.8 wt% dopant contents (Mn1-, Mn2-, and Mn3-TiO2) were synthesized on Ti implants to enhance integrin-mediated osteoblastic responses. The Mg-doped and undoped TiO2 nanocoatings served as the control. Mn element was not only successfully incorporated into the TiO2 matrix, but also formed an oxygen-deficient Mn oxide on the nanowire surface. Although the adsorbed fibronectin (Fn) amount on Mn-doped nanocoatings and its unfolded status were slightly attenuated with increasing Mn amount, the interaction between the coating extract and Fn demonstrated a Mn2+-induced unfolding of Fn with the exposure of the RGD motif. Compared to the Mn1-, Mn2- and Mg-doped TiO2 nanocoatings, the Mn3-TiO2 nanocoating significantly upregulated the expression of integrin α5ß1 probably through increasing the ligand-binding affinity of the integrin rather than integrin binding sites in Fn. Consistent with the activation trend of integrin α5ß1, the Mn3-TiO2 nanocoating enhanced cell adhesion with the long stretched structure of actin fibers and extensive formation of vinculin focal adhesion spots and upregulated the levels of alkaline phosphatase and osteocalcin activities. Therefore, Mn supplementation of orthopedic implants may be a promising way to improve osteogenesis at the implant surface.
Subject(s)
Integrin alpha5beta1 , Integrins , Manganese , Cell Adhesion , Titanium/pharmacology , Titanium/chemistry , Dietary Supplements , Fibronectins/metabolismABSTRACT
Osseointegration is a prerequisite for the function of dental implants, and macrophage-dominated immune responses triggered by implantation determine the outcome of ultimate bone healing mediated by osteogenic cells. The present study aimed to develop a modified titanium (Ti) surface by covalently immobilizing chitosan-stabilized selenium nanoparticles (CS-SeNPs) to sandblasted, large grit, and acid-etched (SLA) Ti substrates and further explore its surface characteristics as well as osteogenic and anti-inflammatory activities in vitro. CS-SeNPs were successfully prepared by chemical synthesis and characterized their morphology, elemental composition, particle size, and Zeta potential. Subsequently, three different concentrations of CS-SeNPs were loaded to SLA Ti substrates (Ti-Se1, Ti-Se5, and Ti-Se10) using a covalent coupling strategy, and the SLA Ti surface (Ti-SLA) was used as a control. Scanning electron microscopy images revealed different amounts of CS-SeNPs, and the roughness and wettability of Ti surfaces were less susceptible to Ti substrate pretreatment and CS-SeNP immobilization. Besides, X-ray photoelectron spectroscopy analysis showed that CS-SeNPs were successfully anchored to Ti surfaces. The results of in vitro study showed that the four as-prepared Ti surfaces exhibited good biocompatibility, with Ti-Se1 and Ti-Se5 groups showing enhanced adhesion and differentiation of MC3T3-E1 cells compared with the Ti-SLA group. In addition, Ti-Se1, Ti-Se5, and Ti-Se10 surfaces modulated the secretion of pro-/anti-inflammatory cytokines by inhibiting the nuclear factor kappa B pathway in Raw 264.7 cells. In conclusion, doping SLA Ti substrates with a modest amount of CS-SeNPs (1-5 mM) may be a promising strategy to improve the osteogenic and anti-inflammatory activities of Ti implants.
Subject(s)
Chitosan , Nanoparticles , Selenium , Selenium/pharmacology , Titanium/pharmacology , Titanium/chemistry , Chitosan/pharmacology , Surface Properties , Osteogenesis , Anti-Inflammatory Agents/pharmacologyABSTRACT
Titanium (Ti) exhibits superior biocompatibility and mechanical properties but is bioinert, while hydroxyapatite (HA) possesses excellent osteogenesis and is widely used for the modification of Ti surface coatings. However, the synthesis of homogeneous and stable HA on metallic materials is still a major challenge. In this study, porous titanium dioxide nanotube arrays were prepared on Ti surface by anodic oxidation, loaded with calcium and phosphorus precursors by negative pressure immersion, and HA coating was formed by in situ crystallization of calcium and phosphorus on the surface by hydrothermal heating. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and bonding strength were conducted to confirm the surface characteristics of each group. The cell proliferation, mineralization degree, and alkaline phosphatase (ALP) activity of MC3T3-E1 cells on samples were calculated and compared in vitro experiments. Cylindrical samples were implanted into rat femurs to evaluate biocompatibility and osteogenesis in vivo. The results showed that HA crystals successfully synthesized in TiO2 nanotubes, enhancing the bonding strength of HA coating and Ti substrate under negative pressure. Moreover, HA coating on Ti substrate remarkably enhanced cell proliferation and osteogenic differentiation activity in vitro, and improved new bone formation as well as osseointegration in vivo.
Subject(s)
Calcium , Nanotubes , Animals , Rats , Osteogenesis , Titanium/pharmacology , Durapatite/pharmacology , Phosphorus , Surface Properties , Coated Materials, Biocompatible/pharmacology , OsteoblastsABSTRACT
AIM: The osseointegration of dental implants is impaired in patients with osteoporosis, leading to significantly higher failure rates. This study set out to investigate the potential effects of alpha-ketoglutarate (α-KG) on implant osseointegration in an osteoporotic mouse model. MATERIALS AND METHODS: Female C57BL/6 mice received ovariectomy and bilateral first maxillary molar extraction at the age of 7 weeks. Dental implants were inserted 8 weeks after tooth extraction. In one of the groups, α-KG was administered via drinking water throughout the experimental period. Specimens were collected on post-implant days (PIDs) 3, 7, 14, and 21 for micro-CT, histological, and immunohistochemical analyses. At the same time, bone-marrow-derived mesenchymal stem cells (BMMSCs) treated with α-KG were interrogated for osteogenic differentiation, autophagic activity, and apoptosis. RESULTS: α-KG supplementation in drinking water resulted in enhanced dental implant osseointegration in ovariectomized mice, with up-regulated osteogenic and autophagic activity and down-regulated osteoclast differentiation and cell apoptosis. α-KG-treated BMMSCs showed enhanced activity in proliferation, survival, colony formation, and osteogenic differentiation, as well as autophagic activity. CONCLUSIONS: Systemic α-KG supplementation effectively prevents the failure of dental implant osseointegration in mice under an osteoporotic state.
Subject(s)
Dental Implants , Drinking Water , Rats , Mice , Female , Animals , Osseointegration , Osteogenesis , Ketoglutaric Acids/pharmacology , Rats, Sprague-Dawley , Mice, Inbred C57BL , Titanium/pharmacologyABSTRACT
Nanomaterials can be used as elicitors for improving the biosynthesis of secondary metabolites in medicinal plants. The present study was conducted to assay the titanium dioxide-nanoparticles (TiO2-NPs) effects on feverfew (Tanacetum parthenium) as an anti-cancer plant. The study showed that TiO2-NPs application increased the amounts of the main compounds and oxygenated monoterpene in essential oils, thereby causing an improvement in the quantity and quality of the essential oils compared to control. The highest effect was related to 1500 ppm TiO2-NPs concentration. Regarding parthenolide, TiO2-NPs had no positive effect on parthenolide content and the highest content was observed in control. Increasing the concentrations over 1500 ppm resulted in a decrease in chlorophyll content, capitule diameter, flower yield, and harvest index compared to other concentrations and control. Additionally, the results indicated that TiO2-NPs foliar spray reduced flower number, biological yield, fresh weight, and dry weights compared with untreated plants. The increase in quality and content of essential oil and lack of increase in parthenolide content, and reproductive and vegetative characteristics showed that TiO2-NPs mainly affected the content and composition of essential oil. Totally, the application of TiO2-NPs in terms of positive effect on the yield and metabolites (without damaging biological effects) can be recommended and followed up to the concentration of 1000 ppm. Overall, the results indicated that improving the synthesis of valuable medicinal metabolites using TiO2-NPs has promising results depending on the type of species, concentration used and target metabolites.
Subject(s)
Nanoparticles , Oils, Volatile , Tanacetum parthenium/chemistry , Tanacetum parthenium/metabolism , Titanium/pharmacology , Phytochemicals/metabolism , Oils, Volatile/metabolismABSTRACT
Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an Ocimum sanctum leaf extract-mediated green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO2 NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO2 nanoparticles. XRD analysis indicated the crystallinity of TiO2 NPs in anatase form. Microscopic investigation revealed that TiO2 NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO2 NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO2 NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO2 NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO2 NPs containing CS gel in diabetic rats.
Subject(s)
Diabetes Mellitus, Experimental , Hyperglycemia , Nanoparticles , Oils, Volatile , Rats , Animals , Titanium/pharmacology , Ocimum sanctum/metabolism , Diabetes Mellitus, Experimental/drug therapy , Nanoparticles/ultrastructure , Wound Healing , Plant Extracts/pharmacology , Plant Extracts/metabolismABSTRACT
Incurable implant-related infection may cause catastrophic consequences due to the existence of a biofilm that resists the infiltration of host immune cells and antibiotics. Innovative approaches inspired by nanomedicine, e.g., engineering innovative multifunctional bionic coating systems on the surface of implants, are becoming increasingly attractive. Herein, 2D black phosphorus nanosheets (BPs) were loaded onto a hydroxyapatite (HA)-coated metal implant to construct a BPs@HA composite coating. With its photothermal conversion effect and in situ biomineralization, the BPs@HA coating shows excellent performances in ablating the bacterial biofilm and accelerating fracture healing, which were verified through both in vitro and in vivo studies. Moreover, differentially expressed genes of bone formation and bone mesenchymal stem cells (BMSCs) regulated by the BPs@HA coating were identified using absolute quantitative transcriptome sequencing followed by the screening of gene differential expressions. A functional enrichment analysis reveals that the expression of core markers related to BMSC differentiation and bone formation could be effectively regulated by BPs through a metabolism-related pathway. This work not only illustrates the great potential in clinical application of the BPs@HA composite coating to eliminate bacteria and accelerate bone fracture healing but also contributes to an understanding of the underlying molecular mechanism of osteogenesis physiological function regulation based on an analysis of absolute quantitative transcriptome sequencing.
Subject(s)
Fracture Healing , Phosphorus , Phosphorus/pharmacology , Durapatite/pharmacology , Osteogenesis , Biofilms , Acceleration , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Titanium/pharmacologyABSTRACT
Titanium dioxide nanoparticles (TiO2 NPs) were prepared by Caricaceae (Papaya) Shell extracts. The Nanoparticles were analyzed by UV-Vis spectrums, X-ray diffractions, and energy-dispersive X-rays spectroscopy analyses with a scanning electron microscope. An antifungal study was carried out for TiO2 NP in contradiction of S. sclerotiorums, R. necatrixs and Fusarium classes that verified a sophisticated inhibitions ratio for S. sclerotiorums (60.5%). Germs of pea were individually preserved with numerous concentrations of TiO2 NPs. An experience of TiO2 NPs (20%, 40%, 80% and 100%), as well as mechanisms that instigated momentous alterations in seed germinations, roots interval, shoot lengths, and antioxidant enzymes, were investigated. Associated with controls, the supreme seeds germinations, roots and plant growth were perceived with the treatments of TiO2 NPs. Super-oxide dis-mutase and catalase activities increased because of TiO2 NPs treatments. This advocates that TiO2 Nanoparticles may considerably change antioxidant metabolisms in seed germinations.