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PURPOSE: Without a standard test for pancreatic carcinomas, this highly lethal disease is normally diagnosed at its advanced stage, leading to a low survival rate of patients. Trophoblast cell-surface antigen 2 (Trop-2), a transmembrane glycoprotein, is associated with cell proliferation and highly expressed in most of solid epithelial tumors, including pancreatic cancer. A non-invasive method of imaging Trop-2 would greatly benefit clinical diagnosis and monitoring of pancreatic cancer. In the current study, 89Zr-labeled anti-Trop-2 antibody (AF650) was recruited for the systemic evaluation of Trop-2 as an immunoPET target for pancreatic cancer imaging. METHODS: AF650 was conjugated with desferrioxamine (DFO) and then radiolabeled with 89Zr. Trop-2 expression levels were determined in three pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and AsPC-1) via western blot, flow cytometry, saturation binding assay, and immunofluorescence staining. The targeting capacity of 89Zr-DFO-AF650 was evaluated in mouse models with subcutaneous xenograft of pancreatic cancers via PET imaging and bio-distribution studies. In addition, a Trop-2-positive orthotopic cancer model was recruited for further validating the targeting specificity of 89Zr-DFO-AF650. RESULTS: BxPC-3 cells expressed high levels of Trop-2, while AsPC-1 and MIA PaCa-2 cells expressed low levels of Trop-2. Additionally, 89Zr-DFO-AF650 exhibited high specificity to Trop-2 in BxPC-3 cells (Kd = 22.34 ± 2.509 nM). In subcutaneous xenograft models, about 28.8 ± 7.63%ID/g tracer accumulated in the BxPC-3 tumors at 120 h post injection, which was much higher than those reaching MIA PaCa-2 (6.76 ± 2.08%ID/g) and AsPC-1 (3.51 ± 0.69%ID/g) tumors (n = 4). More importantly, 89Zr-DFO-AF650 could efficiently distinguish primary tumors in the orthotopic BxPC-3 cancer model, showing high correlation between PET imaging and bio-distribution and sensitivity. CONCLUSIONS: 89Zr-DFO-AF650 can be effectively used to detect pancreatic cancer via Trop-2-mediated immunoPET in vivo, clearly revealing the great potential of Trop-2-based non-invasive imaging in pancreatic cancer detection and treatment monitoring.
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Neoplasias Pancreáticas , Trofoblastos , Animais , Antígenos de Superfície , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Trofoblastos/metabolismo , Trofoblastos/patologia , ZircônioRESUMO
Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair 90/86Y, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with 86Y-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 ± 1.7 and 1.5 ± 0.5, respectively), unprecedented for inorganic nanomaterials. 90Y-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.
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Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Porosidade , Medicina de Precisão , Dióxido de SilícioRESUMO
Hepatic ischemia-reperfusion injury (IRI), which mainly results from excessive reactive oxygen species (ROS) generated by a reperfusion burst of oxygen, has long been a major cause of liver dysfunction and failure after surgical procedures. Here, a monodispersed hydrophilic carbohydrate-derived nanoparticle (C-NP) was synthesized as a nanoantioxidant that could effectively prevent hepatic IRI. The spherical C-NPs had a size of â¼78 ± 11.3 nm covered with polar surface groups. They were well dispersible in water with good colloidal stability, nontoxicity, and good ROS scavenging capability. The C-NPs also exhibited good circulation lifetime, effective delivery to liver, and gradual degradability with an ability to assist the IRI group maintaining a normal and healthy liver status. The pathology mechanism of C-NPs in hepatic IRI was confirmed to be scavenging of excessive ROS by C-NPs. The effective therapeutic treatment of C-NPs in living animals revealed a great potential in clinical prevention for hepatic IRI.
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Nanopartículas , Traumatismo por Reperfusão , Animais , Carboidratos , Fígado , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controleRESUMO
Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed. Overexpression of tissue factor (TF) has been associated with increased tumor growth, angiogenesis, and metastasis in many malignancies, including pancreatic cancer. Herein, we propose the use of a TF-targeted monoclonal antibody (ALT836) conjugated with the pair 86/90Y as a theranostic agent against pancreatic cancer. For methods, serial PET imaging with 86Y-DTPA-ALT836 was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing mice. 90Y-DTPA-ALT836 was employed as a therapeutic agent that also allowed tumor burden monitoring through Cherenkov luminescence imaging. The results were that the uptake of 86Y-DTPA-ALT836 in BXPC-3 xenograft tumors was high and increased over time up to 48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence Imaging. In therapeutic studies, 90Y-DTPA-ALT836 was found to slow tumor growth relative to the control groups and had significantly smaller (p < 0.05) tumor volumes 1 day p.i. Histological analysis of ex vivo tissues revealed significant damage to the treated tumors. The conclusion is that the use of the 86/90Y theranostic pair allows PET imaging with excellent tumor-to-background contrast and treatment of TF-expressing pancreatic tumors with promising therapeutic outcomes.
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Anticorpos Monoclonais/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tromboplastina/antagonistas & inibidores , Radioisótopos de Ítrio/farmacocinética , Animais , Anticorpos Monoclonais/farmacocinética , Linhagem Celular Tumoral , Feminino , Camundongos , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons , Distribuição TecidualRESUMO
Acute kidney injury (AKI) is frequently associated with oxidative stress and causes high mortality annually in clinics. Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for the treatment of AKI. Herein, a novel biomedical use of the endogenous biopolymer melanin as a theranostic natural antioxidant defense nanoplatform for AKI is reported. In this study, ultrasmall Mn2+-chelated melanin (MMP) nanoparticles are easily prepared via a simple coordination and self-assembly strategy, and further incorporated with polyethylene glycol (MMPP). In vitro experiments reveal the ability of MMPP nanoparticles to scavenge multiple toxic reactive oxygen species (ROS) and suppress ROS-induced oxidative stress. Additionally, in vivo results from a murine AKI model demonstrate preferential renal uptake of MMPP nanoparticles and a subsequent robust antioxidative response with negligible side effects according to positron emission tomography/magnetic resonance (PET/MR) bimodal imaging and treatment assessment. These results indicate that the effectiveness of MMPP nanoparticles for treating AKI suggests the potential efficacy of melanin as a natural theranostic antioxidant nanoplatform for AKI, as well as other ROS-related diseases.
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Hydroxyapatite nanowires exhibit a great potential in biomedical applications owing to their high specific surface area, high flexibility, excellent mechanical properties, and similarity to mineralized collagen fibrils of natural bone. In this work, zinc-containing nanoparticle-decorated ultralong hydroxyapatite nanowires (Zn-UHANWs) with a hierarchical nanostructure have been synthesized by a one-step solvothermal method. The highly flexible Zn-UHANWs exhibit a hierarchical rough surface and enhanced specific surface area as compared with ultralong hydroxyapatite nanowires (UHANWs). To evaluate the potential application of Zn-UHANWs in bone regeneration, the biomimetic Zn-UHANWs/chitosan (CS) (Zn-UHANWs/CS) composite porous scaffold with 80â wt % Zn-UHANWs was prepared by incorporating Zn-UHANWs into the chitosan matrix by the freeze-drying process. The as-prepared Zn-UHANWs/CS composite porous scaffold exhibits enhanced mechanical properties, highly porous structure, and excellent water retention capacity. In addition, the Zn-UHANWs/CS porous scaffold has a good biodegradability with the sustainable release of Zn, Ca, and P elements in aqueous solution. More importantly, the Zn-UHANWs/CS porous scaffold can promote the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells and facilitate in vivo bone regeneration as compared with the pure CS porous scaffold or UHANWs/CS porous scaffold. Thus, both the Zn-UHANWs and Zn-UHANWs/CS porous scaffold developed in this work are promising for application in bone defect repair.
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Regeneração Óssea , Osso e Ossos/metabolismo , Quitosana/química , Durapatita/química , Nanocompostos/química , Nanofios/química , Zinco/química , Adesão Celular , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Humanos , Fenômenos Mecânicos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanocompostos/ultraestrutura , Osteogênese , Porosidade , Alicerces TeciduaisRESUMO
Highly flexible multifunctional biopaper comprising ultralong hydroxyapatite nanowires and chitosan (UHANWs/CS), with high weight fractions of ultralong hydroxyapatite nanowires (UHANWs) up to 100â wt. %, is reported. The as-prepared UHANWs/CS composite biopaper has high flexibility and superior mechanical properties even when the weight fraction of UHANWs is as high as 90â wt. %. In contrast, the control samples consisting of hydroxyapatite nanorods and chitosan (HANRs/CS) with weight fractions of HANRs higher than 66.7â wt.% cannot be obtained in the form of the flexible membrane. The ultimate tensile strength and Young's modulus of the UHANWs/CS composite biopaper are about 3.2â times and 4.3â times those of the HANRs/CS membrane with the same weight fraction of HAP, respectively. In addition, the UHANWs/CS composite biopaper (90â wt. % UHANWs) can be used for color printing using a commercial ink-jet printer. The surface wettability, swelling ratio, and water vapor transmission rate of the UHANWs/CS composite biopaper are adjustable by changing the addition amount of UHANWs. In vitro experiments indicate that the UHANWs/CS composite biopaper has good degradability, high acellular bioactivity and high biocompatibility. The as-prepared UHANWs/CS composite biopaper is therefore promising for various biomedical applications such as wound dressing, bone-fracture fixation, and bone-defect repair.
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The templated synthesis of hydroxyapatite (HAP) nanowires@metal-organic framework (MOF) core/shell nanofibers (named HAP@MIL-100(Fe) nanofibers) is demonstrated. The ultralong hydroxyapatite nanowires are adopted as a hard template for the nucleation and growth of MIL-100(Fe) (a typical MOF) through the layer-by-layer method. The Coulombic and chelation interactions between Ca2+ ions on the surface of the HAP nanowires and the COO- organic linkers of MIL-100(Fe) play key roles in the formation process. The as-prepared, water-stable HAP@MIL-100(Fe) nanofibers exhibit peroxidase-like activity toward the oxidation of different peroxidase substrates in the presence of H2 O2 , accompanied by a clear color change of the solution. Furthermore, a flexible, recyclable HAP@MIL-100(Fe) test paper is prepared successfully by using HAP@MIL-100(Fe) nanofibers as building blocks. A simple, low-cost, and sensitive colorimetric method for the detection of H2 O2 and glucose is established based on the as-prepared, flexible, recyclable HAP@MIL-100(Fe) test paper. More importantly, the HAP@MIL-100(Fe) test paper can be recovered easily for reuse by simply dipping in absolute ethanol for just 30â min, thus showing excellent recyclability. With its combination of advantages such as easy transportation, easy storage and use, rapid recyclability, light weight, and high flexibility, this HAP@MIL-100(Fe) test paper is promising for wide applications in various fields.
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Durapatita/química , Estruturas Metalorgânicas/química , Nanofibras/química , Nanofios/química , Peroxidase/química , Ácido Ascórbico/análise , Bioensaio/métodos , Cálcio/química , Glucose/análise , Peróxido de Hidrogênio/análise , Oxirredução , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Propriedades de Superfície , Termogravimetria/métodos , Água/químicaRESUMO
A highly flexible and free-standing paper with high antibacterial activity made from silver nanoparticle (AgNP)-decorated ultralong hydroxyapatite nanowires (HAPNWs) is reported. The HAPNWs@AgNPs nanocomposites were obtained from a facile one-step solvothermal process and utilized for the construction of highly flexible and free-standing inorganic paper through a simple vacuum-filtration procedure. The structure and properties of the HAPNWs@AgNPs paper were characterized in detail. Scanning electron microscope (SEM) and transmission electron microscope (TEM) micrographs show that AgNPs are highly dispersed and stabilized in the nanocomposite and exhibit a narrow particle size distribution. The effects of the concentration of silver nitrate, solvothermal temperature and time on the product were systematically investigated. This method is simple, convenient and reproducible. The as-prepared HAPNWs@AgNPs paper shows long-time sustained silver-ion release, high antibacterial activity against both Gram-negative and Gram-positive bacteria, and good biocompatibility. Overall, this work provides a novel pathway for the preparation of a new type of highly flexible, free-standing and antibacterial inorganic paper made from silver nanoparticle-decorated hydroxyapatite nanowires for various applications, as a promising functional biomaterial.
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Antibacterianos/síntese química , Durapatita/química , Durapatita/síntese química , Nanopartículas Metálicas/química , Nanocompostos/química , Nanofios/química , Prata/química , Antibacterianos/química , Bactérias Gram-Positivas , Microscopia Eletrônica de TransmissãoRESUMO
A facile and environmentally friendly approach has been developed to prepare yolk-shell porous microspheres of calcium phosphate by using calcium L-lactate pentahydrate (CL) as the calcium source and adenosine 5'-triphosphate disodium salt (ATP) as the phosphate source through the microwave-assisted hydrothermal method. The effects of the concentration of CL, the microwave hydrothermal temperature, and the time on the morphology and crystal phase of the product are investigated. The possible formation mechanism of yolk-shell porous microspheres of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and ibuprofen (IBU) are used to explore the application potential of yolk-shell porous microspheres of calcium phosphate in protein/drug loading and delivery. The experimental results indicate that the as-prepared yolk-shell porous microspheres of calcium phosphate have relatively high protein/drug loading capacity, sustained protein/drug release, favorable pH-responsive release behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the yolk-shell porous microspheres of calcium phosphate have promising applications in various biomedical fields such as protein/drug delivery.
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Trifosfato de Adenosina/química , Compostos de Cálcio/química , Fosfatos de Cálcio/química , Hemoglobinas/química , Lactatos/química , Proteínas/química , Animais , Bovinos , Sistemas de Liberação de Medicamentos , Ibuprofeno/química , Teste de Materiais , Microesferas , PorosidadeRESUMO
In recent years, glucose oxidase (GOx) has aroused great research interest in the treatment of diseases related to abnormal glucose metabolisms like cancer and diabetes. However, as a kind of endogenous oxido-reductase, GOx suffers from poor stability and system toxicity in vivo. In order to overcome this bottleneck, GOx is encapsulated in calcium-based biomaterials (CaXs) such as calcium phosphate (CaP) and calcium carbonate (CaCO3) by using it as a biotemplate to simulate the natural biomineralization process. The biomineralized GOx holds improved stability and reduced side effects, due to the excellent bioactivity, biocompatibitliy, and biodegradability of CaXs. In this review, the state-of-the-art studies on GOx-mineralized CaXs are introduced with an emphasis on their application in various biomedical fields including disease diagnosis, cancer treatment, and diabetes management. The current challenges and future perspectives of GOx-mineralized CaXs are discussed, which is expected to promote further studies on these smart GOx-mineralized CaXs biomaterials for practical applications.
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Gas therapy is an emerging "green" cancer treatment strategy; however, its outcome often restricted by the complexity, diversity, and heterogeneity of tumor. Herein, a tumor targeting and tumor microenvironment-activated calcium phosphate nanotheranostic system (denoted as GCAH) is constructed for effective synergistic cancer starvation/gas therapy. GCAH is obtained by a facile biomineralization strategy using glucose oxidase (GOx) as a biotemplate, followed by loading of l-Arginine (L-Arg) and modification of hyaluronic acid (HA) to allow special selectivity for glycoprotien CD44 overexpressed cancer cells. This nanotheranostic system not only exhausts the glucose nutrients in tumor region by the GOx-triggered glucose oxidation, the generated H2 O2 can oxidize L-Arg into NO under acidic tumor microenvironment for enhanced gas therapy. As such, there are significant enhancement effects of starvation therapy and gas therapy through the cascade reactions of GOx and L-Arg, which yields a remarkable synergistic therapeutic effect for 4T1 tumor-bearing mice without discernible toxic side effects.
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Nanopartículas , Neoplasias , Animais , Fosfatos de Cálcio , Glucose Oxidase , Peróxido de Hidrogênio , Camundongos , Microambiente TumoralRESUMO
BACKGROUND: The efficacy of cancer immunotherapy can be limited by the poor immunogenicity of cancer and the immunosuppressive tumor microenvironment (TME). Immunologically programming the TME and creating an immune-inflamed tumor phenotype is critical for improving the immune-responsiveness of cancers. Here, we interrogate the immune modulator Flagrp170, engineered via incorporation of a pathogen-associated molecular pattern (ie, flagellin) into an immunostimulatory chaperone molecule, in transforming poorly immunogenic tumors and establishing a highly immunostimulatory milieu for immune augmentation. METHODS: Multiple murine cancer models were used to evaluate the immunostimulatory activity, antitumor potency, and potential side effects of Flagrp170 on administration into the tumors using a replication impaired adenovirus. Antibody neutralization and mice deficient in pattern recognition receptors, that is, toll-like receptor 5 (TLR5) and NOD like receptor (NLR) family caspase activation and recruitment domain (CARD) domain-containing protein 4 (NLRC4), both of which can recognize flagellin, were employed to understand the immunological mechanism of action of the Flagrp170. RESULTS: Intratumoral delivery of mouse or human version of Flagrp170 resulted in robust inhibition of multiple malignancies including head and neck squamous cell carcinoma and breast cancer, without tissue toxicities. This in situ Flagrp170 treatment induced a set of cytokines in the TME known to support Th1/Tc1-dominant antitumor immunity. Additionally, granulocyte macrophage colony-stimulating factor derived from mobilized CD8+ T cells was involved in the therapeutic activity of Flagrp170. We also made a striking finding that NLRC4, not TLR5, is required for Flagrp170-mediated antitumor immune responses. CONCLUSION: Our results elucidate a novel immune-potentiating activity of Flagrp170 via engaging the innate pattern recognition receptor NLRC4, and support its potential clinical use to reshape cancer immune phenotype for overcoming therapeutic resistance.
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Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/terapia , Proteínas de Ligação ao Cálcio/genética , Flagelina/genética , Proteínas de Choque Térmico HSP70/genética , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adenoviridae/genética , Animais , Anticorpos Neutralizantes/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Linfócitos T CD8-Positivos/metabolismo , Feminino , Flagelina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Camundongos , Proteínas Recombinantes , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Receptor 5 Toll-Like/genética , Resultado do Tratamento , Microambiente Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium-doped carbon quantum dots (SeCQDs) have broad-spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS-related diseases.
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One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Durapatita/química , Selênio/química , Selênio/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Nanofios/química , Papel , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The mononuclear phagocyte system (MPS, e.g., liver, spleen) is often treated as a "blackbox" by nanoresearchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, this imperfection is exploited by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)-related disease. Ceria nanoparticles (NPs) are selected as a representative nano-antioxidant and the detailed mechanism of preventing IRI is investigated. It is found that ceria NPs effectively alleviate the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines are then significantly reduced and the recruitment and infiltration of neutrophils are minimized, which suppress subsequent inflammatory reaction involved in the liver. The protective effect of nano-antioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.
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Cério/química , Cério/farmacologia , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Nanomedicina , Nanopartículas/química , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Cério/farmacocinética , Citocinas/metabolismo , Fígado/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Distribuição TecidualRESUMO
The synthetic bone grafts that mimic the composition and structure of human natural bone exhibit great potential for application in bone defect repair. In this study, a biomimetic porous nanocomposite consisting of ultralong hydroxyapatite nanowires (UHANWs) and collagen (Col) with 66.7 wt% UHANWs has been prepared by the freeze drying process and subsequent chemical crosslinking. Compared with the pure collagen as a control sample, the biomimetic UHANWs/Col porous nanocomposite exhibits significantly improved mechanical properties. More significantly, the rehydrated UHANWs/Col nanocomposite exhibits an excellent elastic behavior. Moreover, the biomimetic UHANWs/Col porous nanocomposite has a good degradable performance with a sustained release of Ca and P elements, and can promote the adhesion and spreading of mesenchymal stem cells. The in vivo evaluation reveals that the biomimetic UHANWs/Col porous nanocomposite can significantly enhance bone regeneration compared with the pure collagen sample. After 12 weeks implantation, the woven bone and lamellar bone are formed throughout the entire UHANWs/Col porous nanocomposite, and connect directly with the host bone to construct a relatively normal bone marrow cavity, leading to successful osteointegration and bone reconstruction. The as-prepared biomimetic UHANWs/Col porous nanocomposite is promising for applications in various fields such as bone defect repair.
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In the past decade, ultralight materials such as aerogels have become one of the hottest research topics owing to their unique properties. However, most reported ultralight materials are bioinert. In this work, by using biocompatible, monodisperse, single-crystalline hydroxyapatite (HAP) microtubes as the building blocks, ultralight, strong, highly porous, three-dimensional (3-D) HAP networks have been successfully fabricated through a facile freeze-drying method and subsequent sintering at 1300 °C for 2 h. The as-prepared ultralight, strong, highly porous 3-D HAP microtube networks exhibit superior properties, such as ultrahigh porosity (89% to 96%), low density (94.1 to 347.1 mg/cm3), high compressive strength that can withstand more than 6400 times of their own weight without any fracture and is higher than aerogels with similar densities, and ultralow thermal conductivity (0.05 W/mK). Owing to their high porosity, ultralight, and good mechanical properties and high biocompatibility, the HAP microtube networks reported herein are promising for applications in various fields.
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Highly flexible hydroxyapatite/collagen (HAP/Col) composite membranes are regarded to be significant for guided bone regeneration application owing to their similar chemical composition to that of natural bone, excellent bioactivity and good osteoconductivity. However, the mechanical strength of the HAP/Col composite membranes is usually weak, which leads to difficult surgical operations and low mechanical stability during the bone healing process. Herein, highly flexible ultralong hydroxyapatite nanowires/collagen (UHANWs/Col) composite biopaper sheets with weight fractions of UHANWs ranging from 0 to 100 % are facilely synthesized. The UHANWs are able to weave with each other to construct a three-dimensional fabric structure in the collagen matrix, providing a strong interaction between UHANWs and an intermolecular force between UHANWs and the collagen matrix. The as-prepared UHANWs/Col composite biopaper exhibits improved mechanical properties and high flexibility. More importantly, the as-prepared highly flexible 70â wt % UHANWs/Col composite biopaper exhibits an excellent cytocompatibility and outstanding cellular attachment performance as compared with the pure collagen and 70â wt % HAP nanorods/Col membranes. In consideration of its superior mechanical properties and outstanding cellular attachment performance, the as-prepared UHANWs/Col composite biopaper is promising for applications in various biomedical fields such as guided bone regeneration.
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A new strategy is proposed based on inhibition of ion transport by lipid bilayer derived from spontaneous assembly of lipopolysaccharides (LPS), thereby a colorimetric method is established for analysis of LPS. At acidic pH values, LPS can specially bind with aminophenylboronic acid modified assembled magnetic nanospheres (APBA/AMNSs), resulting in formation of lipid bilayer around APBA/AMNSs. Under acidic condition, the lipid bilayer can inhibit the release of iron ions from AMNSs into the solution so as to decrease the oxidized extent of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt mediated by hydrogen peroxide. Using the established method, LPS can be detected over the wide linear detection range with the low detection limit. With good selectivity, reproductivity, and simplicity, the method is accurate in LPS tests of real drinking samples.