Preparation and cytotoxicity of doxorubicin-containing gold nanoparticles / 药学实践与服务

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.

In Situ Labeling of Erythrocyte Membrane Anion Channel Proteins with Gold Nanoparticles Observed by Cryo-Scanning Electron Microscopy / 分析化学

Band 3 protein is an important channel protein in the erythrocyte membrane which mediates the anion transport process inside and outside the cell membrane,as well as contributes to the maintenance of erythrocyte morphology,and has important physiological functions.However,the distribution state of this protein in the primary cell membrane is not known.Cryo-scanning electron microscopy enables imaging of the surface morphology of biological samples in a near-physiological state.In order to investigate the distribution of band 3 protein on erythrocyte membranes under physiological conditions,the present study utilized 5-nm gold nanoparticles modified with the antibodies to specifically bind to the band 3 protein on human blood erythrocyte membranes and imaged them by cryo-scanning electron microscopy,to obtain distribution of band 3 protein on human blood erythrocyte membranes.The results showed that the membrane proteins on the erythrocyte membranes tended to be clustered and distributed to form ″protein islands″,and band 3 proteins were mainly distributed in these protein islands,which were tightly connected with each other to form several functional microregions to play their respective roles.

Advances in the characterization of gold nanoparticles and their application in biosensing systems / 国际检验医学杂志

Gold nanoparticles(AuNPs)present unique physicochemical characteristics,excellent biocom-patibility and ease of surface functionalization,which have become the research hotspots in the field of biosens-ing.This article reviews the synthesis methods,main properties and surface functionalization of AuNPs,as well as the research progress of application in various sensing platforms.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Research progress on the application of metal nanoenzymes in the prevention and treatment of plaque biofilm-associated oral diseases / 口腔疾病防治

@#Oral plaque biofilms are one of the bases for the survival and metabolism of different bacteria. With the emergence of drug-resistant bacteria due to antibiotic abuse, the prevention and treatment of plaque biofilm-associated oral diseases are becoming increasingly difficult. Although some research progress has been made in the field of biofilm formation and destruction, there is still a lack of effective clinical therapies for plaque biofilm-associated oral diseases. Metal nanoenzymes possess the physical properties of nanoparticles and exhibit catalytic activity similar to that of natural enzymes. The nanoscale size of metal nanoenzymes provides a greater specific surface area to help reactive oxygen species spread rapidly to active catalytic sites and improve the antioxidant properties of nanoenzymes. Additionally, metal nanoenzymes are easy to produce using different methods, such as electrochemical reduction, solvent thermal synthesis and microwave-assisted synthesis. Moreover, metal nanoenzymes can produce a high concentration of hydroxyl radicals, catalyze plaque biofilm degradation, lyse glucan and inhibit biofilm formation by oxidative stress reactions, as well as kill bacteria by releasing metal ions. Thus, metal nanoenzymes are expected to become a new option for the prevention and treatment of oral plaque biofilm-associated diseases. However, metal nanoenzymes can enter organisms through oral, intravenous and respiratory routes, triggering potential toxic effects such as pulmonary toxicity, hepatotoxicity and neurotoxicity. In a complex biological environment, the occurrence of metal nanoenzymes toxicity may involve multiple mechanisms, and the mechanism of action and safety need to be thoroughly investigated. In this paper, we intend to describe the research progress on metal nanoenzymes through an overview of their properties, antibacterial mechanisms, biotoxicity and applications in the prevention and treatment of oral plaque biofilm-related diseases, which may provide new ideas for the prevention and treatment of these diseases.

Effect and mechanism of reactive oxygen species-responsive nanoparticles on the regulation of human gingival fibroblast function and inflammation induced by lipopolysaccharide / 口腔疾病防治

Objective@#To investigate the effects of PssL-NAC reactive oxygen species (ROS)-responsive nanoparticles on intracellular ROS production, inflammatory factor levels, collagen production, cell function and Toll-like receptor 4 (TLR4), NF-κB nuclear factor-κB (p65) pathway protein expression in human gingival fibroblasts (HGFs) induced by Porphyromonas gingivalis-lipopolysaccharide (P.g-LPS).@*Methods@#This study was reviewed and approved by the ethics committee. PssL-NAC microspheres containing oil soluble antioxidant N-acetylcysteine (NAC) were obtained by connecting the hydrophobic end of polycaprolactone (PCL) and the hydrophilic end of polyethylene glycol (PEG) via thioketal (TK) bonds in response to ROS, and self loading in the aqueous and oil phases. After preparation of the PssL-NAC microspheres and aqueous NAC solution, successful synthesis of the nanoparticles was verified by transmission electron microscopy. Then, HGFs were exposed to P.g-LPS (0, 5, or 10 μg/mL), P.g-LPS (0, 5, or 10 μg/mL)+NAC, and P.g-LPS (0, 5, or 10 μg/mL)+PssL-NAC, and the ROS levels in the different groups were observed under confocal microscopy to determine the concentration of P.g-LPS for use in subsequent experiments. The groups were as follows: control group (no treatment), P.g-LPS group (HGFs treated with P.g-LPS), NAC group (HGFs treated with P.g-LPS and NAC), and PssL-NAC group (HGFs treated with P.g-LPS and PssL-NAC). Cell counting kit-8 (CCK-8) assays verified the biosafety of PssL-NAC. The ROS levels in the different groups were detected by DCFH-DA probes and observed via confocal microscopy. Real-time qPCR (RT-qPCR) was used to monitor the gene expression levels of the intracellular inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), collagen 1 (COL1) and collagen 3 (COL3). The effect of PssL-NAC on the migration of HGFs was observed via the scratch test. The protein expression of TLR4-NF-κB, and phosphorylated p65 (p-p65) in the TLR4-NF-κB pathway was evaluated by Western blot.@*Results@#PssL-NAC had no significant effect on HGF proliferation (P>0.05). At elevated P.g-LPS concentrations, PssL-NAC maintained intracellular ROS levels approximately twice those in the control group (P<0.001). PssL-NAC significantly decreased P.g-LPS-induced IL-6 (P<0.001) and TNF-α (P<0.001) gene expression and increased COL1 gene expression (P<0.001). After P.g-LPS stimulation, PssL-NAC restored cell migration to the control level (P>0.05) and decreased the protein expression of TLR4 (P<0.001), p65 (P = 0.006), and p-p65 (P = 0.017) in the TLR4-NF-κB pathway.@*Conclusion@#PssL-NAC maintains the appropriate intracellular ROS concentration, alleviates P.g-LPS-induced inflammation in HGFs through the TLR4-NF-κB pathway, and restores the cell functions of collagen production and migration in an inflammatory environment.

Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats / 中国药理学通报

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

Role of cerium oxide nanoparticles in doxorubicin-induced cardiotoxicity and its effect on P53 gene expression / 中国现代医生

@#Objective To study the effect of nano-ceria on doxorubicin-induced cardiotoxic injury and its effect on P53 gene expression,and to explore the mechanism of nano-ceria on doxorubicin-induced cardiotoxic injury.Methods H9C2 myocardial cells were cultured and randomly divided into five groups:control group,model group(1μmol/L adriamycin),nano-cerium oxide group(10μg/ml nano-cerium oxide),experimental group(1μmol/L adriamycin +10μg/ml nano-cerium oxide),and positive control group(1μmol/L adriamycin+10μmol/L dexperimine).The adriamycin induced cardiotoxicity model was established,and the viability of myocardial cells was measured by CCK-8 method.The contents of lactate dehydrogenase(LDH)and malondialdehyde(MDA)in myocardial cells were detected by biochemical method.The levels of reactive oxygen(ROS)and the apoptosis rate in myocardial cells were detected by flow cytometry.The expressions of Bax,Bcl-2 and P53 proteins in myocardial cells were detected by Western blot.Results Compared with the control group,the cell viability was decreased in the model group,the cell LDH and MDA contents were increased,the intracellular ROS level and apoptosis rate were increased,the expressions of Bax and P53 proteins were increased,and the expression of Bcl-2 protein was decreased,and the ratio of Bcl-2/Bax was decreased(all P<0.001).Compared with the model group,the experimental group showed increased cell viability,decreased cell LDH and MDA contents,decreased cell ROS content and apoptosis rate,decreased Bax and P53 protein expressions,and increased Bcl-2 protein expression,and the Bcl-2/Bax ratio was increased(all P<0.001).Conclusion Ceria nanoparticles can effectively prevent adriamycin-induced cardiotoxic injury,and its effect may be related to the down-regulation of P53 gene to inhibit cardiomyocyte apoptosis.

Conformational Engineering of Antibody Fragments on The Surface of Platinum Nanoparticles / 生物化学与生物物理进展

ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.

The Application in The Development of Immunoassay Based on Upconversion Nanomaterials / 生物化学与生物物理进展

Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.

Bactericidal Effect of Selenium Nanoparticles Combined with Povidone-iodine on Pathogenic Bacteria in Surgical Site Infection / 中山大学学报(医学科学版)

ObjectiveTo investigate the bactericidal effect of loaded multifunctional povidoneiodine-nanometer selenium （PVP-I@Se） disinfectant on Staphylococcus aureus （SA） and methicillin-resistant Staphylococcus aureus （MRSA）， and to provide an experimental basis for the reduction of surgical site infection （SSI）. MethodsThe control group was the povidone iodine （PVP-I） group with different concentrations of iodine （50， 75， 100， 200 and 400 μg/mL）. The PVP-I@Se group （experimental group） was the PVP-I group further supplemented with 2 μg/mL Selenium nanoparticles （SeNPs）. Then we compared the bactericidal effect of the two groups of disinfectant solutions on SA and MRSA by examining the minimum inhibitory concentration （MIC）， minimum bactericidal concentration （MBC）， the shortest sterilization time at a concentration of 50 μg/mL iodine and the inhibition zone diameters at concentrations of 200 μg/mL and 400 μg/mL iodine. ResultsMIC values of PVP-I against SA and MRSA were both 79.17 μg/mL， and those of PVP-I@Se were 54.17 and 70.83 μg/mL， respectively. MBC values of PVP-I against SA and MRSA were 129.17 and 150.00 μg/mL， respectively， and those of PVP-I@Se were 70.83 and 87.50 μg/mL， respectively. At a concentration of 50 μg/mL iodine， the shortest sterilization time of PVP-I for SA and MRSA was 130 s and 140 s， respectively， and that of PVP-I@Se was 65 s and 75 s， respectively. At a concentration of 200 μg/ml iodine， the inhibition zone diameters of PVP-I for SA and MRSA were 7.67 mm and 8.33 mm， and those of PVP-I@Se were both 9.50 mm. At a concentration of 400 μg/mL iodine， the inhibition zone diameters of PVP-I for SA and MRSA were 9.00 mm and 9.33 mm， and those of PVP-I@Se were 11.67 mm and 12.00 mm， respectively. ConclusionsPVP-I with different concentrations of 50， 75， 100， 200 and 400 μg/mL iodine supplemented with 2 μg/mL SeNPs have better and faster bactericidal effect on SA and MRSA. When combined with SeNPs， PVP-I can enhance the bactericidal activity against SA and MRSA， but with better sensitizing effect on SA than MRSA and higher demand of iodine concentration （400 μg/mL） for sensitizing effect on MRSA. This study provides a theoretical basis for selecting optimal concentration and action time of the disinfectant， thus reducing SSI.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Study on the role of nano antibacterial materials in orthodontics (a review) / Estudo sobre o papel dos materiais nanoantibacterianos na ortodontia

Nanoparticles (NPs) are insoluble particles with a diameter of fewer than 100 nanometers. Two main methods have been utilized in orthodontic therapy to avoid microbial adherence or enamel demineralization. Certain NPs are included in orthodontic adhesives or acrylic resins (fluorohydroxyapatite, fluorapatite, hydroxyapatite, SiO2, TiO2, silver, nanofillers), and NPs (i.e., a thin layer of nitrogen-doped TiO2 on the bracket surfaces) are coated on the surfaces of orthodontic equipment. Although using NPs in orthodontics may open up modern facilities, prior research looked at antibacterial or physical characteristics for a limited period of time, ranging from one day to several weeks, and the limits of in vitro studies must be understood. The long-term effectiveness of nanotechnology-based orthodontic materials has not yet been conclusively confirmed and needs further study, as well as potential safety concerns (toxic effects) associated with NP size.

Nanopartículas (NPs) são partículas insolúveis com diâmetro inferior a 100 nanômetros. Dois métodos principais têm sido utilizados na terapia ortodôntica para evitar a aderência microbiana ou a desmineralização do esmalte: NPs são incluídas em adesivos ortodônticos ou resinas acrílicas (fluoro-hidroxiapatita, fluorapatita, hidroxiapatita, SiO2, TiO2, prata, nanopreenchimentos) e NPs são revestidas nas superfícies de equipamentos ortodônticos, ou seja, uma camada fina de TiO2 dopado com nitrogênio nas superfícies do braquete. Embora o uso de NPs em ortodontia possa tornar acessível modernos recursos, pesquisas anteriores analisaram as características antibacterianas ou físicas por um período limitado de tempo, variando de 24 horas a várias semanas, por isso devem ser compreendidos os limites dos estudos in vitro. A eficácia de longo prazo de materiais ortodônticos com base em nanotecnologia ainda não foi confirmada de forma conclusiva, o que exige mais estudos, bem como potenciais preocupações de segurança (efeitos tóxicos) associadas ao tamanho da NP.

Influence of the addition of nanohydroxyapatite to scaffolds on proliferation and differentiation of human mesenchymal stem cells: a systematic review of in vitro studies

One of the main challenges of tissue engineering in dentistry is to replace bone and dental tissues with strategies or techniques that simulate physiological tissue repair conditions. This systematic review of in vitro studies aimed to evaluate the influence of the addition of nanohydroxyapatite (NHap) to scaffolds on cell proliferation and osteogenic and odontogenic differentiation of human mesenchymal stem cells. In vitro studies on human stem cells that proliferated and differentiated into odontogenic and osteogenic cells in scaffolds containing NHap were included in this study. Searches in PubMed/MEDLINE, Scopus, Web of Science, OpenGrey, ProQuest, and Cochrane Library electronic databases were performed. The total of 333 articles was found across all databases. After reading and analyzing titles and abstracts, 8 articles were selected for full reading and extraction of qualitative data. Results showed that despite the large variability in scaffold composition, NHap-containing scaffolds promoted high rates of cell proliferation, increased alkaline phosphatase (ALP) activity during short culture periods, and induced differentiation, as evidenced by the high expression of genes involved in osteogenesis and odontogenesis. However, further studies with greater standardization regarding NHap concentration, type of scaffolds, and evaluation period are needed to observe possible interference of these criteria in the action of NHap on the proliferation and differentiation of human stem cells.

Niobium oxyhydroxide as a bioactive agent and reinforcement to a high-viscosity bulk-fill resin composite

Abstract Objective The present in vitro study incorporated niobium oxyhydroxide fillers into an experimental high-viscosity bulk-fill resin composite to improve its mechanical performance and provide it a bioactive potential. Methodology Scanning electron microscopy synthesized and characterized 0.5% niobium oxyhydroxide fillers, demonstrating a homogeneous morphology that represented a reinforcement for the feature. Fillers were weighed, gradually added to the experimental resin composite, and homogenized for one minute, forming three groups: BF (experimental high-viscosity bulk-fill resin composite; control), BF0.5 (experimental high-viscosity bulk-fill resin composite modified with 0.5% niobium oxyhydroxide fillers), and BFC (commercial bulk-fill resin composite Beautifil Bulk U, Shofu; positive control). In total, 10 specimens/groups (8 × 2 × 2 mm) underwent flexural strength (FS) tests in a universal testing machine (Instron) (500N). Resin composites were also assessed for Knoop hardness (KH), depth of cure (DoC), degree of conversion (DC), elastic modulus (E), and degree of color change (ΔE). The bioactive potential of the developed resin composite was evaluated after immersing the specimens into a simulated body fluid in vitro solution and assessing them using a Fourier-transformed infrared spectroscope with an attenuated total reflectance accessory. One-way ANOVA, followed by the Tukey's test (p<0.05), determined FS, DC, KH, and ΔE. For DoC, ANOVA was performed, which demonstrated no significant difference between groups (p<0.05). Conclusions The high-viscosity bulk-fill resin composite with 0.5% niobium oxyhydroxide fillers showed promising outcomes as reinforcement agents and performed well for bioactive potential, although less predictable than the commercial resin composite with Giomer technology.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Study on the role of nano antibacterial materials in orthodontics (a review)

Abstract Nanoparticles (NPs) are insoluble particles with a diameter of fewer than 100 nanometers. Two main methods have been utilized in orthodontic therapy to avoid microbial adherence or enamel demineralization. Certain NPs are included in orthodontic adhesives or acrylic resins (fluorohydroxyapatite, fluorapatite, hydroxyapatite, SiO2, TiO2, silver, nanofillers), and NPs (i.e., a thin layer of nitrogen-doped TiO2 on the bracket surfaces) are coated on the surfaces of orthodontic equipment. Although using NPs in orthodontics may open up modern facilities, prior research looked at antibacterial or physical characteristics for a limited period of time, ranging from one day to several weeks, and the limits of in vitro studies must be understood. The long-term effectiveness of nanotechnology-based orthodontic materials has not yet been conclusively confirmed and needs further study, as well as potential safety concerns (toxic effects) associated with NP size.

Resumo Nanopartículas (NPs) são partículas insolúveis com diâmetro inferior a 100 nanômetros. Dois métodos principais têm sido utilizados na terapia ortodôntica para evitar a aderência microbiana ou a desmineralização do esmalte: NPs são incluídas em adesivos ortodônticos ou resinas acrílicas (fluoro-hidroxiapatita, fluorapatita, hidroxiapatita, SiO2, TiO2, prata, nanopreenchimentos) e NPs são revestidas nas superfícies de equipamentos ortodônticos, ou seja, uma camada fina de TiO2 dopado com nitrogênio nas superfícies do braquete. Embora o uso de NPs em ortodontia possa tornar acessível modernos recursos, pesquisas anteriores analisaram as características antibacterianas ou físicas por um período limitado de tempo, variando de 24 horas a várias semanas, por isso devem ser compreendidos os limites dos estudos in vitro. A eficácia de longo prazo de materiais ortodônticos com base em nanotecnologia ainda não foi confirmada de forma conclusiva, o que exige mais estudos, bem como potenciais preocupações de segurança (efeitos tóxicos) associadas ao tamanho da NP.

Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studie

Evaluation of the Implant Success Rate of Titanium-based Implant Materials: A Systematic Review and Meta-Analysis

ABSTRACT Objective: To investigate the success of implants, the increase of bone integration, and the effect of nanostructure/nanoparticles as Titanium-based implant materials on the success of implants. The present study evaluated the implant success rate of Titanium-based implant materials. Material and Methods: PICO: Population (dental implant), intervention (coated titanium implant surface), comparison (uncoated titanium implant surface), and outcome (bone-implant contact) were considered as a search strategy tool and study inclusion criteria. Searches for systematic literature were conducted on databases from Scopus, Science Direct, PubMed, ISI, Web of Knowledge, and Embase until 12 December 2022. Modified CONSORT Criteria (Reporting guidelines for preclinical in vitro studies on dental materials) were used to evaluate the quality of studies. The fixed effect model and inverse-variance method were used to calculate the 95% confidence interval for mean differences. Stata/MP V. 17 software was used to conduct the meta-analysis. Results: After reviewing the abstracts of 97 articles, studies not related to the inclusion criteria were excluded, and ten studies were selected from the remaining 39 studies after reviewing the full text. The mean difference in boneimplant contact between coated and uncoated dental implants was 0.25 (MD, 0.25 95% CI 0.01, 0.49;p=0.04). Conclusion: The titanium implant surface with nano coating can increase bone-implant contact and cause bone integration.

Preparation of Lir@BSA-PMF nanoparticles and verification of their cell functions / 基础医学与临床

Objective To synthesize bovine serum albumin(BSA)-loaded liraqlutide(Lir)-nanoparticles coated with platelet membrane fragments(PMF)using a"bottom-up"nano-engineering chemistry technique,and to evaluate their cyto-compatibility and potential function of anti-oxidative stress.Methods PMF was extracted as reported previously.Lir@BSA nanoparticles were prepared by self-assembly method.PMF was coated on the sur-face of Lir@BSA nanoparticles by co-extrusion to prepare Lir@BSA-PMF.The physical and chemical properties of Lir@BSA-PMF particles were characterized as particle size,Zeta potential,transmission electron microscopy and particle size stability.The encapsulation efficiency,loading efficiency and cumulative release efficiency of liraglu-tide were calculated by enzyme-linked immunosorbent assay.Further,SDS-PAGE was used to analyze whether there was a similar membrane protein distribution of platelet membrane on Lir@BSA-PMF bionicnanocarrier.CCK-8 assay was used to verify the biocompatibility of the materials.Reactive oxygen species(ROS)experi-ment was used to explore the effect of Lir@BSA-PMF on cell oxidative damage.The uptake of cells on Lir@BSA-PMF bionic nano capsules was verified by cell phagocytosis experiment.Results Lir@BSA-PMF nanop-articles had a stable particle size of 25 nm with a spherical morphology,and a Zeta potential value of-25.5 mV.The encapsulation efficiency,loading efficiency and cumulative release efficiency of liraglutide were 85.56％,7.96％and 77.06％,respectively.SDS-PAGE analysis showed that the Lir@BSA-PMF bio-mimetic nano capsules retained the similar membrane protein distribution as platelet membrane.CCK-8 assay verified that the nanomaterials were non-cytotoxic.ROS results showed that Lir@BSA-PMF nanomaterials had obvious antioxidant properties.The results of cell phagocytosis showed that the cells had a good phagocytosis effect on Lir@BSA-PMF nanoparticles.Conclusions The nanoparticles Lir@BSA-PMF are successfully syn-thesized and have no effects on cells viability in vitro.The particles are taken up by cells and show a significant function of antioxidant damage.