RESUMEN
Breakthroughs in actual clinical applications have begun through vaccine-based cancer immunotherapy, which uses the body's immune system, both humoral and cellular, to attack malignant cells and fight diseases. However, conventional vaccine approaches still face multiple challenges eliciting effective antigen-specific immune responses, resulting in immunotherapy resistance. In recent years, biomimetic nanovaccines have emerged as a promising alternative to conventional vaccine approaches by incorporating the natural structure of various biological entities, such as cells, viruses, and bacteria. Biomimetic nanovaccines offer the benefit of targeted antigen-presenting cell (APC) delivery, improved antigen/adjuvant loading, and biocompatibility, thereby improving the sensitivity of immunotherapy. This review presents a comprehensive overview of several kinds of biomimetic nanovaccines in anticancer immune response, including cell membrane-coated nanovaccines, self-assembling protein-based nanovaccines, extracellular vesicle-based nanovaccines, natural ligand-modified nanovaccines, artificial antigen-presenting cells-based nanovaccines and liposome-based nanovaccines. We also discuss the perspectives and challenges associated with the clinical translation of emerging biomimetic nanovaccine platforms for sensitizing cancer cells to immunotherapy.
Asunto(s)
Células Presentadoras de Antígenos , Vacunas contra el Cáncer , Inmunoterapia , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia/métodos , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Nanopartículas/administración & dosificación , Células Presentadoras de Antígenos/inmunología , Biomimética/métodos , Materiales Biomiméticos/administración & dosificación , Animales , Liposomas , NanovacunasRESUMEN
Piezoelectric nanogenerator (PENG) produces stable electrical signals in response to external mechanical stimuli and holds promise in the fields of flexible sensors and smart wearable devices. In practice, a high-performance PENG with a straightforward structure and exceptional reliability is deeply desired. This study optimally synthesizes piezoelectric composites comprising polyvinylidene fluoride (PVDF) incorporated with barium titanate (BTO) nanoparticles (NPs) and fabricated a PENG with heightened sensitivity by using the electrospinning technique. The polar ß-phase content of the dual-optimized BTO-PVDF (barium titanate and polyvinylidene fluoride) electrospun fiber reaches up to 82.39%. In the bending mode, it achieves a remarkable maximum open-circuit voltage of 19.152 V, a transferred charge of 8.058 nC, and an output voltage per unit area of 2.128 V cm- 2. Under vertical pressure conditions, the BP-PENG exhibits an impressive voltage of 12.361 V while the force is 2.156 N, demonstrating a notable pressure sensing sensitivity of 5.159 V kPa-1, with an excellent linear relationship. Furthermore, the BP-PENG displays sensitive sensing features in monitoring hand movements. The sensitive response and high performance make it promising for applications in human motion monitoring and smart wearable devices.
Asunto(s)
Polímeros de Fluorocarbono , Nanofibras , Polivinilos , Humanos , Bario , Reproducibilidad de los Resultados , ElectricidadRESUMEN
BACKGROUND: The infrazygomatic crest mini-screw has been widely used, but the biomechanical performance of mini-screws at different insertion angles is still uncertain. The aim of this study was to analyse the primary stability of infrazygomatic crest mini-screws at different angles and to explore the effects of the exposure length (EL), screw-cortical bone contact area (SCA), and screw-trabecular bone contact area (STA) on this primary stability. METHODS: Ninety synthetic bones were assigned to nine groups to insert mini-screws at the cross-combined angles in the occlusogingival and mesiodistal directions. SCA, STA, EL, and lateral pull-out strength (LPS) were measured, and their relationships were analysed. Twelve mini-screws were then inserted at the optimal and poor angulations into the maxillae from six fresh cadaver heads, and the same biomechanical metrics were measured for validation. RESULTS: In the synthetic-bone test, the LPS, SCA, STA, and EL had significant correlations with the angle in the occlusogingival direction (rLPS = 0.886, rSCA = -0.946, rSTA = 0.911, and rEL= -0.731; all P < 0.001). In the cadaver-validation test, significant differences were noted in the LPS (P = 0.011), SCA (P = 0.020), STA (P = 0.004), and EL (P = 0.001) between the poor and optimal angulations in the occlusogingival direction. The STA had positive correlations with LPS (rs = 0.245 [synthetic-bone test] and r = 0.720 [cadaver-validation test]; both P < 0.05). CONCLUSIONS: The primary stability of the infrazygomatic crest mini-screw was correlated with occlusogingival angulations. The STA significantly affected the primary stability of the infrazygomatic crest mini-screw, but the SCA and EL did not.
Asunto(s)
Tornillos Óseos , Hueso Esponjoso , Hueso Cortical , Humanos , Hueso Cortical/anatomía & histología , Fenómenos Biomecánicos , Hueso Esponjoso/anatomía & histología , Métodos de Anclaje en Ortodoncia/instrumentación , Métodos de Anclaje en Ortodoncia/métodos , Cadáver , Cigoma/cirugía , Cigoma/anatomía & histología , Maxilar/anatomía & histología , Análisis del Estrés DentalRESUMEN
BACKGROUND: Kümmell's disease is a special type of osteoporotic vertebral fracture that causes chronic low back pain and deformity, which seriously affects the living quality of patients. PVP is commonly used to treat osteoporotic vertebral fractures and can quickly relieve low back pain. So, the objective of this study was to analyze the clinical efficacy and experience of bipedicular percutaneous vertebroplasty combined with postural reduction for the treatment of Kümmell's disease. METHODS: A retrospective analysis of patients with Kümmell's disease who underwent bipedicular percutaneous vertebroplasty was conducted from February 2016 to May 2018. Operative time, VAS, bone cement injection volume, cement leakage rate, compression improvement of vertebral front edge and vertebral center, and correction degree of kyphosis were collected and analyzed meticulously. RESULTS: The operative time was 45.33 ± 7.64 min. The volume of bone cement injected was 5.38 ± 1.33 ml. The compression improvement of vertebral front edge was 7.31 ± 1.21%. The compression improvement of vertebral center was 10.34 ± 1.15% and the correction degree of kyphosis was - 2.73 ± 0.31ã. Bone cement leakage occurred in 6 of 39 patients (15.38%), but no clinical symptoms were observed. The VAS scores were significantly lower at 1 day after the surgery, 6 months and at the last follow-up than before the surgery (P = 0.000, respectively). The VAS score was lower at the last follow-up than at 1 day after the surgery (P = 0.001). CONCLUSION: Bipedicular percutaneous vertebroplasty combined with postural reduction could achieve satisfactory analgesic effect in the treatment of Kümmell's disease, and restore the height of the vertebral body and improve kyphosis to some extent.
Asunto(s)
Fijación de Fractura/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Osteonecrosis/cirugía , Fracturas de la Columna Vertebral/cirugía , Vertebroplastia/métodos , Anciano , Anciano de 80 o más Años , Cementos para Huesos , Dolor Crónico/diagnóstico , Dolor Crónico/etiología , Dolor Crónico/cirugía , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Femenino , Estudios de Seguimiento , Fijación de Fractura/efectos adversos , Humanos , Cifosis/diagnóstico , Cifosis/etiología , Cifosis/cirugía , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Osteonecrosis/complicaciones , Osteonecrosis/diagnóstico , Dimensión del Dolor , Radiografía , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico , Fracturas de la Columna Vertebral/etiología , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Columna Vertebral/cirugía , Resultado del Tratamiento , Vertebroplastia/efectos adversosRESUMEN
Biofilms of multidrug-resistant bacteria in chronic wounds pose a great challenge in wound care. Herein, we report the topical delivery of molecularly engineered antimicrobial peptides using electrospun nanofiber dressings as a carrier for the treatment of biofilms of multidrug-resistant bacteria in diabetic wounds. Molecularly engineered human cathelicidin peptide 17BIPHE2 was successfully encapsulated in the core of pluronic F127/17BIPHE2-PCL core-shell nanofibers. The in vitro release profiles of 17BIPHE2 showed an in initial burst followed by a sustained release over 4 weeks. The peptide nanofiber formulations effectively killed methicillin-resistant Staphylococcus aureus (MRSA) USA300. Similarly, the 17BIPHE2 peptide containing nanofibers could also effectively kill other bacteria including Klebsiella pneumoniae (104 to 106 CFU) and Acinetobacter baumannii (104 to 107 CFU) clinical strains in vitro without showing evident cytotoxicity to skin cells and monocytes. Importantly, 17BIPHE2-containing nanofiber dressings without debridement caused five-magnitude decreases of the MRSA USA300 CFU in a biofilm-containing chronic wound model based on type II diabetic mice. In combination with debridement, 17BIPHE2-containing nanofiber dressings could completely eliminate the biofilms, providing one possible solution to chronic wound treatment. Taken together, the biodegradable nanofiber-based wound dressings developed in this study can be utilized to effectively deliver molecularly engineered peptides to treat biofilm-containing chronic wounds.
Asunto(s)
Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Vendajes , Biopelículas/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Nanofibras/administración & dosificación , Ingeniería de Proteínas , Infección de Heridas/tratamiento farmacológico , Administración Cutánea , Animales , Antibacterianos/química , Péptidos Catiónicos Antimicrobianos/química , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Modelos Animales de Enfermedad , Liberación de Fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Nanofibras/química , Poloxámero/química , Poliésteres/química , Piel/efectos de los fármacos , Piel/microbiología , Infección de Heridas/patología , CatelicidinasRESUMEN
PURPOSE: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. METHODS: 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. RESULTS: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. CONCLUSIONS: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.
Asunto(s)
Antibacterianos/metabolismo , Péptidos Catiónicos Antimicrobianos/metabolismo , Calcifediol/administración & dosificación , Preparaciones de Acción Retardada/administración & dosificación , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Calcifediol/química , Línea Celular , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Humanos , Queratinocitos/metabolismo , Monocitos/metabolismo , Poliésteres/química , Pseudomonas aeruginosa/efectos de los fármacos , Células U937 , CatelicidinasRESUMEN
OBJECTIVE: To explore the potential applications of a chamber for in vivo tissue engineering, and to establish a novel model for in vivo tissue-engineered cartilage. METHODS: Four experimental groups were included in this study: (A) chambers + chondrocytes/collagen gel; (B) chambers + chondrocytes/PLGA gel; (C) chondrocytes/collagen gel alone; and (D) chondrocytes/PLGA gel alone. Groups C and D served as controls. The samples were implanted subcutaneously in the donor rabbit, and the contents were harvested at 8 wk after implantation. RESULTS: Histologic and immunohistochemical staining and RT-PCR results revealed regenerated cartilage-like tissue in group B and small, irregularly shaped islands of opalescent tissue in group A. In contrast, the control groups displayed vascular invasion and inflammatory reaction, which eventually led to fibrosis and absorption. CONCLUSIONS: Reproduced cartilages were obtained in an immunocompetent animal model through the use of a bioinert perforated chamber.
Asunto(s)
Cartílago/citología , Proliferación Celular , Condrocitos/citología , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodos , Animales , Cartílago/metabolismo , Condrocitos/metabolismo , Colágeno/metabolismo , Geles/metabolismo , Ácido Láctico/metabolismo , Masculino , Modelos Animales , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Conejos , Trasplante AutólogoRESUMEN
We have synthesized a biocompatible polyaspartic acid-based polymer (molecular weight approximately 15,000-25,000) with cysteine on its backbone for use as a capping ligand for functionalized Au, Ag, and CdSe@ZnS nanoparticles. Nearly monodisperse, hydrophobic Au and Ag nanoparticles and CdSe@ZnS quantum dots were first prepared in organic solvents via conventional synthesis and then ligand exchanged to derive polymer-coated water-soluble nanoparticles. Multiple thiol groups in the polymer backbone conferred excellent protection against aggregation of the nanoparticles, and the carboxylic acid groups in the polymer provided the possibility of covalent binding with antibodies. Compared to the conventional thiol-based ligands, this polymer coating led to superior colloidal stability under the experimental conditions involved in the bioconjugation and purification steps. Goat antihuman-IgG (anti-h-IgG) and antimouse epidermal growth factor receptor (anti-m-EGFR) antibodies were conjugated with the polymer-coated nanoparticles and successfully applied to protein detection. This polymer coating exhibited minimal nonspecific interaction with cells and could be broadly applied to cell labeling.
Asunto(s)
Materiales Biocompatibles/química , Cisteína/química , Péptidos/química , Puntos Cuánticos , Animales , Anticuerpos Inmovilizados/análisis , Anticuerpos Inmovilizados/química , Anticuerpos Inmovilizados/inmunología , Línea Celular Tumoral , Receptores ErbB/inmunología , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/química , RatonesRESUMEN
Ag and CuO in the form of nanoparticles have been widely used in our daily life as antibacterial agents, through releasing Ag ions and generating reactive oxygen species (ROS). In this work, we demonstrate that by synthesizing Ag@CuO nanohybrids with core-shell configurations, their bactericidal activity can be synergistically enhanced compared to the respective constituents. Upon AM 1.5G light illumination for short durations, the measured minimum inhibitory concentrations of the Ag@CuO nanohybrids show a significant decrease against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains, requiring only 7% and 34% of those when conducted in the dark. The spread plate results demonstrate that with nanohybrid concentrations of 11.0 and 21.9 mg L-1, at least 7 orders of magnitude decrease in Escherichia coli and Staphylococcus aureus colony forming units is achieved, when the Ag@CuO nanohybrids are exposed to light illumination for 10 min. The effect of illumination is found to induce Ag+ release and enhance 1O2 generation, which act concertedly to facilitate the remarkable photo-enhanced bactericidal effect.
Asunto(s)
Antibacterianos/farmacología , Cobre/farmacología , Escherichia coli/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Plata/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Cobre/química , Relación Dosis-Respuesta a Droga , Iones/química , Iones/farmacología , Pruebas de Sensibilidad Microbiana , Nanoestructuras/química , Tamaño de la Partícula , Procesos Fotoquímicos , Povidona/química , Plata/química , Plata/metabolismo , Propiedades de SuperficieRESUMEN
We demonstrate magnetic capsules with high uptake capacity by combining single-hole hydroxyl-functionalized PEDOT hollow spheres and Fe(3)O(4) nanoparticles; potential applications include pollutant removal and controlled drug delivery.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/química , Óxido Ferrosoférrico/química , Nanopartículas/química , Polímeros/química , Animales , Línea Celular Tumoral , Supervivencia Celular , Sistemas de Liberación de Medicamentos , Humanos , Magnetismo , Ratones , Muramidasa/química , Células 3T3 NIH , Tamaño de la Partícula , Espectrofotometría UltravioletaRESUMEN
PURPOSE: This study aims to explore the presence of informative protein biomarkers in the human saliva proteome and to evaluate their potential for detection of oral squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: Whole saliva samples were collected from patients (n = 64) with OSCC and matched healthy subjects (n = 64). The proteins in pooled whole saliva samples of patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation, capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry, and Mascot sequence database searching. Immunoassays were used for validation of the candidate biomarkers on a new group of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating characteristic analysis was exploited to evaluate the diagnostic value of discovered candidate biomarkers for OSCC. RESULTS: Subtractive proteomics revealed several salivary proteins at differential levels between the OSCC patients and matched control subjects. Five candidate biomarkers were successfully validated using immunoassays on an independent set of OSCC patients and matched healthy subjects. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC. CONCLUSION: Patient-based saliva proteomics is a promising approach to searching for OSCC biomarkers. The discovery of these new targets may lead to a simple clinical tool for the noninvasive diagnosis of oral cancer. Long-term longitudinal studies with large populations of individuals with oral cancer and those who are at high risk of developing oral cancer are needed to validate these potential biomarkers.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de la Boca/metabolismo , Proteómica/métodos , Saliva/metabolismo , Adulto , Biomarcadores , Carcinoma de Células Escamosas/diagnóstico , Electroforesis en Gel Bidimensional , Femenino , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Polímeros/química , Sensibilidad y EspecificidadRESUMEN
Traditional electrospun nanofiber membranes were incapable of promoting cellular infiltration due to its intrinsic property (e.g., dense structure and small pore size) limiting their use in tissue regeneration. Herein, we report a simple and novel approach for expanding traditional nanofiber membranes from two-dimensional to three-dimensional (3D) with controlled thickness and porosity via depressurization of subcritical CO2 fluid. The expanded 3D nanofiber scaffolds formed layered structures and simultaneously maintained the aligned nanotopographic cues. The 3D scaffolds also retained the fluorescent intensity of encapsulated coumarin 6 and the antibacterial activity of encapsulated antimicrobial peptide LL-37. In addition, the expanded 3D nanofiber scaffolds with arrayed holes can significantly promote cellular infiltration and neotissue formation after subcutaneous implantation compared to traditional nanofiber membranes. Such scaffolds also significantly increased the blood vessel formation and the ratio of M2/M1 macrophages after subcutaneous implantation for 2 and 4â¯weeks compared to traditional nanofiber membranes. Together, the presented method holds great potential in the fabrication of functional 3D nanofiber scaffolds for various applications including engineering 3D in vitro tissue models, antimicrobial wound dressing, and repairing/regenerating tissues in vivo. STATEMENT OF SIGNIFICANCE: Electrospun nanofibers have been widely used in regenerative medicine due to its biomimicry property. However, most of studies are limited to the use of 2D electrospun nanofiber membranes. To the best of our knowledge, this article is the first instance of the transformation of traditional electrospun nanofiber membranes from 2D to 3D via depressurization of subcritical CO2 fluid. This method eliminates many issues associated with previous approaches such as necessitating the use of aqueous solutions and chemical reactions, multiple-step process, loss of the activity of encapsulated biological molecules, and unable to expand electrospun nanofiber mats made of hydrophilic polymers. Results indicate that these CO2 expanded nanofiber scaffolds can maintain the activity of encapsulated biological molecules. Further, the CO2 expanded nanofiber scaffolds with arrayed holes can greatly promote cellular infiltration, neovascularization, and positive host response after subcutaneous implantation in rats. The current work is the first study elucidating such a simple and novel strategy for fabrication of 3D nanofiber scaffolds.
Asunto(s)
Materiales Biocompatibles/química , Dióxido de Carbono/farmacología , Células Gigantes/citología , Nanofibras/química , Andamios del Tejido/química , Animales , Cumarinas/química , Nanofibras/ultraestructura , Poliésteres/química , Ratas Sprague-Dawley , Tiazoles/química , Ingeniería de TejidosRESUMEN
Herein, a robust method to fabricate expanded nanofiber scaffolds with controlled size and thickness using a customized mold during the modified gas-foaming process is reported. The expansion of nanofiber membranes is also simulated using a computational fluid model. Expanded nanofiber scaffolds implanted subcutaneously in rats show cellular infiltration, whereas non-expanded scaffolds only have surface cellular attachment. Compared to unexpanded nanofiber scaffolds, more CD68+ and CD163+ cells are observed within expanded scaffolds at all tested time points post-implantation. More CCR7+ cells appear within expanded scaffolds at week 8 post-implantation. In addition, new blood vessels are present within the expanded scaffolds at week 2. The formed multinucleated giant cells within expanded scaffolds are heterogeneous expressing CD68, CCR7, or CD163 markers. Together, the present study demonstrates that the expanded nanofiber scaffolds promote cellular infiltration/tissue integration, a regenerative response, and neovascularization after subcutaneous implantation in rats. The use of expanded electrospun nanofiber scaffolds offers a promising method for in situ tissue repair/regeneration and generation of 3D tissue models/constructs.
Asunto(s)
Nanofibras/administración & dosificación , Nanofibras/química , Neovascularización Fisiológica/efectos de los fármacos , Andamios del Tejido/química , Animales , Antígenos CD/metabolismo , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Biomarcadores/metabolismo , Células Cultivadas , Membranas/efectos de los fármacos , Membranas/metabolismo , Ratas , Regeneración/efectos de los fármacos , Ingeniería de Tejidos/métodosRESUMEN
The Mouse Double Minute 2 (MDM2) oncogene plays a critical role in cancer development and progression through p53-dependent and p53-independent mechanisms. Both natural and synthetic MDM2 inhibitors have been shown anticancer activity against several human cancers. We have recently identified a novel ginsenoside, 25-OCH3-PPD (GS25), one of the most active anticancer ginsenosides discovered thus far, and have demonstrated its MDM2 inhibition and anticancer activity in various human cancer models, including prostate cancer. However, the oral bioavailability of GS25 is limited, which hampers its further development as an oral anticancer agent. The present study was designed to develop a novel nanoparticle formulation for oral delivery of GS25. After GS25 was successfully encapsulated into PEG-PLGA nanoparticles (GS25NP) and its physicochemical properties were characterized, the efficiency of MDM2 targeting, anticancer efficacy, pharmacokinetics, and safety were evaluated in in vitro and in vivo models of human prostate cancer. Our results indicated that, compared with the unencapsulated GS25, GS25NP demonstrated better MDM2 inhibition, improved oral bioavailability and enhanced in vitro and in vivo activities. In conclusion, the validated nano-formulation for GS25 oral delivery improves its molecular targeting, oral bioavailability and anticancer efficacy, providing a basis for further development of GS25 as a novel agent for cancer therapy and prevention.
Asunto(s)
Antineoplásicos/administración & dosificación , Ginsenósidos/administración & dosificación , Nanopartículas/química , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Administración Oral , Animales , Antineoplásicos/farmacología , Células CACO-2 , Línea Celular Tumoral , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Ginsenósidos/farmacología , Humanos , Masculino , Ratones , Nanomedicina , Trasplante de Neoplasias , Poliésteres/química , Polietilenglicoles/química , Distribución Tisular , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Nitrogen fertilizer unabsorbed by crops eventually discharges into the environment through runoff, leaching and volatilization, resulting in three-dimensional (3D) pollution spanning from underground into space. Here we describe an approach for controlling nitrogen loss, developed using loss control fertilizer (LCF) prepared by adding modified natural nanoclay (attapulgite) to traditional fertilizer. In the aqueous phase, LCF self-assembles to form 3D micro/nano networks via hydrogen bonds and other weak interactions, obtaining a higher nitrogen spatial scale so that it is retained by a soil filtering layer. Thus nitrogen loss is reduced and sufficient nutrition for crops is supplied, while the pollution risk of the fertilizer is substantially lowered. As such, self-fabrication of nano-material was used to manipulate the nitrogen spatial scale, which provides a novel and promising approach for the research and control of the migration of other micro-scaled pollutants in environmental medium.
Asunto(s)
Nanoestructuras/química , Nitrógeno/química , Resinas Acrílicas/química , Productos Agrícolas , Contaminación Ambiental , Fertilizantes , Compuestos de Magnesio/química , Nanoestructuras/ultraestructura , Dispersión de Radiación , Compuestos de Silicona/química , Espectroscopía Infrarroja por Transformada de Fourier , Urea/química , Rayos XRESUMEN
Multifunctional nanoparticles combine drug and imaging agent together to assign both therapeutic and diagnostic functions. However, particle aggregation/dissociation and/or major differences in the bio-distribution and targeting capability of drugs and imaging probes are main obstacles for the efficient, coordinated delivery of multiple agents, unless the different agents can be tightly bound and well-protected during their circulation in vivo. In this paper, we report the coordinated in vivo delivery of anti-cancer drugs and imaging agents by chemically loading doxorubicin and magnetite nanocubes (MNs) in the core of polymeric nanoparticles. Living polymerization, nitroxide-mediated radical polymerization (NMP), was applied to construct the optimal polymers to co-deliver doxorubicin and MNs. The resulting diblock polymers consisted of one block with triethylene glycol brushes and another block with carboxylic acid groups to bind doxorubicin and Fe3O4 MNs. The optimal polymer has narrow polydispersity (PDI=1.2) and high doxorubicin/MN loading (30wt.%/28wt.%). Core-shell particles were obtained with good stability and a suitable particle size of ~100nm. The doxorubicin and MNs loaded in this polymeric system showed highly coordinated bio-distribution in the balb/C mice model. This system may have important impact on the design of effective and stable dual-agent co-delivery systems.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Nanopartículas de Magnetita/administración & dosificación , Polímeros/química , Animales , Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Nanopartículas de Magnetita/análisis , Nanopartículas de Magnetita/ultraestructura , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Nanopartículas/ultraestructura , PolimerizacionRESUMEN
Saliva harbors a wide spectrum of proteins that may reflect the health/disease status in the human body. Profiling of the proteins in saliva from a disease population can potentially yield valuable clinical parameters to be used for diagnosis and prognosis of the disease. Advances in proteomic technologies have enabled comprehensive profiling of protein expression in cells, tissue, and body fluids. When applied to readily accessible saliva samples from disease patients for biomarker study, such a global approach allows attaining the most discriminatory protein biomarkers that can best predict the disease status. In this chapter, we describe the protocols for proteomic analysis of saliva using 2D gel electrophoresis, Western blotting, and LC-MS/MS.
Asunto(s)
Proteómica/métodos , Saliva/química , Western Blotting , Cromatografía Liquida , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Espectrometría de Masas en TándemRESUMEN
Poly aryl-ether-ether-ketone (PEEK) is an alternative to metal alloys in orthopedic applications. Although the polymer provides many significant advantages such as excellent mechanical properties and non-toxicity, it suffers from insufficient elasticity and biocompatibility. Since the elastic modulus of diamond-like carbon (DLC) is closer to that of cortical bone than PEEK, the DLC/PEEK combination is expected to enhance the stability and surface properties of PEEK in bone replacements. In this work, PEEK is coated with diamond-like carbon (DLC) by plasma immersion ion implantation and deposition (PIII&D) to enhance the surface properties. X-ray photoelectron spectrometry (XPS), Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy demonstrate successful deposition of the DLC film on PEEK without an obvious interface due to energetic ion bombardment. Atomic force microscopy (AFM) and contact angle measurements indicate changes in the surface roughness and hydrophilicity, and nanoindentation measurements reveal improved surface hardness on the DLC/PEEK. Cell viability assay, scanning electron microscopy (SEM), and real-time PCR analysis show that osteoblast attachment, proliferation, and differentiation are better on DLC/PEEK than PEEK. DLC/PEEK produced by PIII&D combines the advantages of DLC and PEEK and is more suitable for bone or cartilage replacements.
Asunto(s)
Materiales Biocompatibles/química , Carbono/química , Diamante/química , Cetonas/química , Polietilenglicoles/química , Animales , Benzofenonas , Adhesión Celular , Línea Celular , Proliferación Celular , Supervivencia Celular , Módulo de Elasticidad , Humanos , Osteoblastos/citología , Polímeros , Ratas , Propiedades de SuperficieRESUMEN
A series of cationic fluorine-containing amphiphilic graft copolymers P(HFMA-St-MOTAC)-g-PEG comprising poly(hexafluorobutyl methacrylate) (PHFMA) poly(methacryl oxyethyl trimethylammonium chloride) (PMOTAC) polystyrene (PSt) backbones and poly(ethylene glycol) (PEG) side chains are synthesized as a type of non-viral gene vector. The copolymers self-assemble into spherical micelles in the aqueous media and turbidity and cytotoxicity measurements show that those micelles have excellent dispersive stability and low cytotoxicity. The interactions between the copolymers and calf-thymus DNA are studied by fluorescence spectroscopy and viscosity. The former discloses electrostatic interaction, hydrophobic interaction, and hydrogen bonding in the copolymer/DNA system, whereas the latter indicates that these graft copolymers can bind DNA via the electrostatic and classical intercalation modes. The DNA-binding capacity determined by the gel retardation assay and UV-visible spectrophotometry shows that the copolymers have good binding capacity to DNA and a high charge density or HFMA content in the copolymers bode well for DNA-binding. Transmission electron microscopy, photon correlation spectroscopy, and zeta potential data reveal that stable colloidal complexes (particles) can form easily between the copolymer micelles and DNA. Our results suggest that the copolymers are a promising non-viral vector in a gene delivery system.
Asunto(s)
ADN/metabolismo , Portadores de Fármacos/química , Flúor/química , Polímeros/química , Animales , Células CHO , Cationes , Muerte Celular , Cromatografía en Gel , Cricetinae , Cricetulus , Electroforesis en Gel de Agar , Espectroscopía de Resonancia Magnética , Metacrilatos/química , Micelas , Microscopía Electrónica de Transmisión , Polietilenglicoles/química , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , ViscosidadRESUMEN
Development of strontium releasing implants capable of stimulating bone formation and inhibiting bone resorption is a desirable solution for curing osteoporosis. In this work, well-ordered SrTiO(3) nanotube arrays capable of Sr release at a slow rate and for a long time are successfully fabricated on titanium by simple hydrothermal treatment of anodized titania nanotubes. This surface architecture combines the functions of nanoscaled topography and Sr release to enhance osseointegration while at the same time leaving space for loading of other functional substances. In vitro experiments reveal that the SrTiO(3) nanotube arrays possess good biocompatibility and can induce precipitation of hydroxyapatite from simulated body fluids (SBF). This Ti-based implant with SrTiO(3) nanotube arrays is an ideal candidate for osteoporotic bone implants. The proposed method can also be extended to load other biologically useful elements such as Mg and Zn.