RESUMO
Breast cancer was the leading cause of newly diagnosed cases of tumors in 2020, ranking as the second highest cause of female death. Chemotherapy remains the conventional treatment of choice for breast tumors in most clinical cases. However, it is often accompanied by a poor prognosis and severe side effects, resulting from an insufficient accumulation of the drug at tumor sites and an unsystematic distribution of the drug across the body. Inspired by the fact that breast tumor cells overexpress integrin α2ß1 on the surface, we designed and constructed an integrin α2ß1 targeting DGEA-modified liposomal doxorubicin (DGEA-Lipo-DOX) platform for application in breast cancer therapy. The DGEA-Lipo-DOX was stable with a uniform particle size of 121.1 ± 3.8 nm and satisfactory drug encapsulation. Demonstrated in vitro and in vivo, the constructed platform exhibited improved antitumor ability. The DGEA-Lipo-DOX showed 4-fold enhanced blood circulation and 6-fold increased accumulation of DOX at the tumor sites compared to those of free DOX, resulting in a significantly enhanced antitumor efficacy in tumor-bearing mice. A preliminary safety evaluation suggested that the systemic toxicity of DOX was relieved by DGEA-Lipo delivery. Collectively, binding integrin α2ß1 by DGEA may represent an alternative therapeutic strategy for potentially safer breast cancer treatment.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/prevenção & controle , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos , Integrina alfa2beta1/antagonistas & inibidores , Oligopeptídeos/química , Animais , Antibióticos Antineoplásicos/química , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Humanos , Integrina alfa2beta1/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Ratos Sprague-Dawley , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Template-based strategies are becoming increasingly important for controlling the position of nanoparticle-based (NP-based) structures on surfaces for a wide variety of encoding and device fabrication strategies. Thus, there is an increasing need to understand the behavior of NPs in confined spaces. Herein, a systematic investigation of the diffusion and adsorption properties of DNA-modified NPs is presented in lithographically defined, high-aspect-ratio pores using a template-confined, DNA-mediated assembly. Leveraging the sequence-specific binding affinity of DNA, it is discovered that although NP adsorption in deep polymer pores follows a traditional Langmuir adsorption model when under thermodynamic control, such NPs kinetically follow Fick's classical law of diffusion. Importantly, these observations allow one to establish design rules for template-confined, DNA-mediated NP assembly on substrates based on pore dimensions, NP size and shape, NP concentration, temperature, and time. As a proof-of-concept example, these design rules are used to engineer a vertical, four-layer assembly consisting of individual octahedral NPs stacked on top of one another, with in-plane positioning defined by pores generated by e-beam lithography.
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Ouro/química , Nanopartículas Metálicas/química , Adsorção , Cinética , Polímeros/química , TermodinâmicaRESUMO
Origami is a topic of rapidly growing interest in both the scientific and engineering research communities due to its promising potential in a broad range of applications. Previous assembly approaches of origami structures at the micro/nanoscale are constrained by the applicable classes of materials, topologies and/or capability of control over the transformation. Here, we introduce an approach that exploits controlled mechanical buckling for autonomic origami assembly of 3D structures across material classes from soft polymers to brittle inorganic semiconductors, and length scales from nanometers to centimeters. This approach relies on a spatial variation of thickness in the initial 2D structures as an effective strategy to produce engineered folding creases during the compressive buckling process. The elastic nature of the assembly scheme enables active, deterministic control over intermediate states in the 2D to 3D transformation in a continuous and reversible manner. Demonstrations include a broad set of 3D structures formed through unidirectional, bidirectional, and even hierarchical folding, with examples ranging from half cylindrical columns and fish scales, to cubic boxes, pyramids, starfish, paper fans, skew tooth structures, and to amusing system-level examples of soccer balls, model houses, cars, and multi-floor textured buildings.
RESUMO
Alloy nanoparticles are important in many fields, including catalysis, plasmonics, and electronics, due to the chemical and physical properties that arise from the interactions between their components. Typically, alloy nanoparticles are made by solution-based synthesis; however, scanning-probe-based methods offer the ability to make and position such structures on surfaces with nanometer-scale resolution. In particular, scanning probe block copolymer lithography (SPBCL), which combines elements of block copolymer lithography with scanning probe techniques, allows one to synthesize nanoparticles with control over particle diameter in the 2-50 nm range. Thus far, single-element structures have been studied in detail, but, in principle, one could make a wide variety of multicomponent systems by controlling the composition of the polymer ink, polymer feature size, and metal precursor concentrations. Indeed, it is possible to use this approach to synthesize alloy nanoparticles comprised of combinations of Au, Ag, Pd, Ni, Co, and Pt. Here, such structures have been made with diameters deliberately tailored in the 10-20 nm range and characterized by STEM and EDS for structural and elemental composition. The catalytic activity of one class of AuPd alloy nanoparticles made via this method was evaluated with respect to the reduction of 4-nitrophenol with NaBH4. In addition to being the first catalytic studies of particles made by SPBCL, these proof-of-concept experiments demonstrate the potential for SPBCL as a new method for studying the fundamental science and potential applications of alloy nanoparticles in areas such as heterogeneous catalysis.
Assuntos
Ligas/química , Nanopartículas Metálicas/química , Metais/química , Nanotecnologia/métodos , Catálise , Cobalto/química , Ouro/química , Nanopartículas Metálicas/ultraestrutura , Níquel/química , Nitrofenóis/química , Oxirredução , Paládio/química , Platina/química , Polímeros/química , Prata/químicaRESUMO
A novel, apertureless, cantilever-free pen array can be used for dual scanning photochemical and molecular printing. Serial writing with light is enabled by combining self-focusing pyramidal pens with an opaque backing between pens. The elastomeric pens also afford force-tuned illumination and simultaneous delivery of materials and optical energy. These attributes make the technique a promising candidate for maskless high-resolution photopatterning and combinatorial chemistry.
Assuntos
Nanotecnologia/métodos , Polímeros/química , Impressão/métodos , Técnicas de Química Combinatória , Desenho de Equipamento , Tinta , Luz , Nanopartículas Metálicas/química , Microscopia de Fluorescência , Nanotecnologia/instrumentação , Óptica e Fotônica , Tamanho da Partícula , Impressão/instrumentação , Propriedades de Superfície , Raios UltravioletaRESUMO
OBJECTIVE: To investigate the expression patterns of E-cadherin and P-cadherin in murine-tooth germs at early developmental stages. METHODS: Mandible samples of CD1 mice from embryonic day 12.5 to postnatal day 3.5 were collected. The expressions of E-cadherin and P-cadherin in murine mandibular first molar germs were detected by immunofluorescence and observed under confocal fluorescence microscope. HE staining was performed for tissue morphology. RESULTS: Both E-cadherin and P-cadherin were widely expressed in the epithelial tissues through early developmental stages. The E-cadherin expression was increased in polarizing pre-ameloblasts, whereas the P-cadherin expression declined. The expression of the P-cadherin could be detected in epithelial tissues before bud stage, and expressed in mature ameloblasts at secretory stage. CONCLUSION: The E-cadherin and P-cadherin expressed in different spatiotemporal expression patterns, indicating their individual functions during tooth development. P-cadherin might function in the secretion and mineralization of enamel.
Assuntos
Caderinas/metabolismo , Odontogênese , Germe de Dente/metabolismo , Ameloblastos/metabolismo , Animais , Esmalte Dentário , Expressão Gênica , Camundongos , Dente MolarRESUMO
Background: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells. Methods: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system. Results: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 µg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78±1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78±5.93%). Conclusion: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.
Assuntos
Antineoplásicos , Venenos Elapídicos , Lipossomos , Lipossomos/química , Concentração de Íons de Hidrogênio , Animais , Venenos Elapídicos/química , Venenos Elapídicos/farmacologia , Humanos , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Camundongos , Apoptose/efeitos dos fármacos , Liberação Controlada de Fármacos , Citotoxinas/química , Citotoxinas/farmacologia , Citotoxinas/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Distribuição Tecidual , Microambiente Tumoral/efeitos dos fármacos , Nanopartículas/químicaRESUMO
Cholesterol is an indispensable component of most liposomes, heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo. On the other hand, as an active ingredient, AA can decrease TGF-ß secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.
Assuntos
Colesterol , Doxorrubicina/análogos & derivados , Lipossomos , Triterpenos Pentacíclicos , Camundongos , Animais , Linhagem Celular Tumoral , PolietilenoglicóisRESUMO
A novel SERS membrane is synthesized by combining metal lattice and surface enhanced Raman scattering (SERS) technology. Since R6G is a carcinogenic and harmful pollutant, and traditional detection methods have many drawbacks and have research value, this paper selects R6G as the detection target. The SERS substrates are synthesized by loading Au nanoparticles (Au NPs) on the surface of polyvinylidene fluoride (PVDF) membrane. The Au NPs are synthesized through a controllable hydrothermal method. The synthesized AuNPs are covered by some gold particles, forming a fold pattern. Finally, the synthesized structure is immobilized on the surface of the PVDF membrane by the phase inversion method. It is suggested that the prepared Au NPs@PVDF membrane exhibits adjustable cavity structure, strong plasmon coupling, tunable magnetic plasmon resonance, prominent SERS performances. The prepared Au NPs@PVDF membrane showed sensitive SERS activity, good mechanical strength and reusability, expanding the application field of SERS detection. Overall, this study establishes a novel technique for the synthesis of SERS membrane with excellent SERS property and expands the application field of SERS detection.
Assuntos
Ouro , Nanopartículas Metálicas , Polímeros de Fluorcarboneto , Ouro/química , Nanopartículas Metálicas/química , Polivinil , Prata/química , Análise Espectral Raman/métodosRESUMO
It is essential to synthesize a "diagnosis and therapy" integration nanocarrier for magnetic resonance imaging-guided breast cancer-targeted chemotherapy. Here, we report Fe3O4/P(NIPAM-AA-MAPEG) nanogels (MNLs) based on in situ loading of doxorubicin (DOX) by miniemulsion polymerization. Especially, propyl acrylic acid (AA) moieties were introduced to absorb DOX by electrostatic interactions and conjugated with the antibody herceptin (HER) through the amino-carboxyl coupling reaction. The size and morphology of MNLs could be adjusted by varying the polymerization parameters, such as the monomer feeding ratio, ferrofluid content, and cross-linker content. The MNLs showed superior stability in a physiological environment, but their structures were destroyed in an acidic environment to accelerate DOX release. The dissociation of the HER-DOX-MNLs accelerated the delivery of DOX and enhanced the therapeutic effects. The studies exhibited that the HER-DOX-MNLs could inhibit the tumor growth. In addition, the MNLs with a high magnetic content had the potential advantages in magnetic resonance imaging (MRI) of breast cancer diagnosis. The dual-targeted pH-responsive nanogels were successfully designed as a multifunctional nanocarrier for realizing HER2-positive breast cancer chemotherapy and diagnostics.
Assuntos
Doxorrubicina , Neoplasias , Acrilatos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Imageamento por Ressonância Magnética , Nanogéis , Neoplasias/tratamento farmacológico , Trastuzumab/farmacologiaRESUMO
Burning lignocellulosic biomass wastes in an outdoor atmosphere has placed heavy burden on ecological environment and increased risk on human health. Converting solid agricultural wastes into functional materials is a research hotspot. In this study, N-doped and CoO-loaded carbocatalyst (CoO-N/BC) was successfully synthesized from the cotton stalk biomass via a simple synthesis process of impregnation and carbonization. Compared with cotton stalk biomass derived pristine biochar, the CoO-N/BC possessed a higher specific surface area (466.631 m2 g-1vs 286.684 m2 g-1) as well as a better catalytic performance in the activation of peroxymonosulfate (PMS) for CIP degradation. The superior catalytic efficiency was ascribed to the directional flow of electrons on the well-organized carbon network of CoO-N/BC, which accelerated electron migration and improved electron conduction ability. Based on the results of radical quenching experiment and electron paramagnetic resonance (EPR), both radical and non-radical process conjointly led to the stepwise decomposition of CIP, and singlet oxygen (1O2) mediated non-radical pathway was discovered to play a dominant role. Besides, the carbon-bridge mediated non-radical pathway was proved to accelerate this degradation process through the experiments of prolong the time of adding CIP at different time intervals. Nitrogen doped sites and CoO active sites as well as defects formed in sp2-hybridized carbon network were supposed to be the active sites for PMS. Furthermore, EIS and LSV were employed to confirm the electron transfer mediated non-radical process of reaction system. This work provides a modified strategy for the disposition of lignocellulosic biomass wastes and illuminates the underlying mechanism of heterogeneous catalysis by CoO-N/BC.
Assuntos
Ciprofloxacina , Peróxidos , Biomassa , Humanos , LigninaRESUMO
Triple-negative breast cancer is often aggressive and resistant to various cancer therapies, especially corresponding targeted drugs. It is shown that targeted delivery of chemotherapeutic drugs to tumor sites could enhance treatment outcome against triple-negative breast cancer. In this study, we exploited the active tumor-targeting capability of macrophages by loading doxorubicin-carrying liposomes on their surfaces via biotin-avidin interactions. Compared with conventional liposomes, this macrophage-liposome (MA-Lip) system further increased doxorubicin accumulation in tumor sites, penetrated deeper into tumor tissue, and enhanced antitumor immune response. As a result, the MA-Lip system significantly lengthened the survival rate of 4T1 cell-bearing mice with low toxicity. Besides, the MA-Lip system used highly biocompatible and widely approved materials, which ensured its long-term safety. This study provides a system for triple-negative breast cancer treatment and offers another macrophage-based strategy for tumor delivery.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Feminino , Lipossomos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , MacrófagosRESUMO
This study aimed to investigate the in vivo dissolution of tricalcium silicate (Ca3 SiO5 , C3 S) bone cement in the rabbit femoral defect. Results indicated that C3 S paste directly integrated with the bone tissue without the protection of the bone-like apatite. Calcium silicate hydrate gel (C-S-H gel) and Ca(OH)2 were the main components of C3 S paste. The dissolution model of C3 S paste was a mass loss rather than a decrease in volume. The initial dissolution of C3 S paste (0 ~ 6 weeks) was greatly attributed to the release of Ca(OH)2 , and the later dissolution (>6 weeks) was attributed to the decalcification of C-S-H gel. Although the mass of C3 S paste could decrease by more than 19 wt % after 6 weeks of implantation, the created pores (<1 µm) were not large enough for the bone tissue to migrate into C3 S paste. The loss of Ca ions also resulted in the transformation of SiO4 tetrahedrons from Q1 and Q2 to Q0 , Q3 , and Q4 in C-S-H gel. Because only isolated SiO4 tetrahedrons (Q0 ) and Ca ions could be absorbed by the bone tissue, C3 S paste gradually transformed into a silica-rich gel. The fundamental reason for no decrease in volume of C3 S paste was that the SiO4 tetrahedron network still maintained the frame structure of C3 S paste during the implantation.
Assuntos
Cimentos Ósseos , Compostos de Cálcio/química , Silicatos/química , Animais , Desenvolvimento Ósseo , Osso e Ossos/anatomia & histologia , Hidróxido de Cálcio/química , Géis , Porosidade , Coelhos , Solubilidade , Microtomografia por Raio-XRESUMO
Size expansion can effectively improve tumor accumulation of nanocarriers where precise control is required. A dual-responsive nanocarrier stimulated by both endogenous pH and exogenous heat stimuli can change its size. Herein, a nanoparticle composed of poly(N,N-diethyl acrylamide) (PDEAA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) is developed. The antitumor drug celastrol (CLT) and the photosensitizer indocyanine green (ICG) are then loaded in it to form CIPP. ICG generates heat under near-infrared (NIR) stimulation to kill tumor cells and enhance CIPP penetration. Meanwhile, CIPP expands in response to hyperthermia and acid tumor microenvironments, preventing itself from returning to the blood flow, thus accumulating in tumor sites. Ultimately, the acidic lysosomal environment in tumor cells disintegrates CIPP to release CLT, directly inducing immunogenic cell death and sensitizing tumor cells for hyperthermia by disrupting the interaction of heat shock protein 90 and P50cdc37. Most of the tumors in B16F10-bearing mice are eradicated after single laser irradiation. The dual-responsive CIPP with multiple functions and simple design displays a synergistic antitumor effect. This study provides a basis for developing size-expandable stimulus-responsive drug delivery systems against tumors.
Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Acrilamidas/síntese química , Acrilamidas/química , Acrilamidas/farmacocinética , Acrilamidas/toxicidade , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Terapia Combinada , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Tratamento Farmacológico , Feminino , Verde de Indocianina/química , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/uso terapêutico , Raios Infravermelhos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Nanopartículas/toxicidade , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/uso terapêutico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Polímeros/síntese química , Polímeros/química , Polímeros/farmacocinética , Polímeros/toxicidade , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacocinética , Ácidos Polimetacrílicos/toxicidadeRESUMO
Bmp2 is essential for dentin development and formation. Bmp2 conditional knock-out (KO) mice display a similar tooth phenotype of dentinogenesis imperfecta (DGI). To elucidate a foundation for subsequent functional studies of cross talk between mRNAs and lncRNAs in Bmp2-mediated dentinogenesis, we investigated the profiling of lncRNAs and mRNAs using immortalized mouse dental Bmp2 flox/flox (iBmp2fx/fx) and Bmp2 knock-out (iBmp2ko/ko) papilla cells. RNA sequencing was implemented to study the expression of the lncRNAs and mRNAs. Quantitative real-time PCR (RT-qPCR) was used to validate expressions of lncRNAs and mRNAs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict functions of differentially expressed genes (DEGs). Protein-protein interaction (PPI) and lncRNA-mRNA co-expression network were analyzed by using bioinformatics methods. As a result, a total of 22 differentially expressed lncRNAs (16 downregulated vs 6 upregulated) and 227 differentially expressed mRNAs (133 downregulated vs. 94 upregulated) were identified in the iBmp2ko/ko cells compared with those of the iBmp2fx/fx cells. RT-qPCR results showed significantly differential expressions of several lncRNAs and mRNAs which were consistent with the RNA-seq data. GO and KEGG analyses showed differentially expressed genes were closely related to cell differentiation, transcriptional regulation, and developmentally relevant signaling pathways. Moreover, network-based bioinformatics analysis depicted the co-expression network between lncRNAs and mRNAs regulated by Bmp2 in mouse dental papilla cells and symmetrically analyzed the effect of Bmp2 during dentinogenesis via coding and non-coding RNA signaling.
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BACKGROUND: Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. METHODS: Throat swabs were collected from children with HFMD and suspected HFMD during 2010-2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. RESULTS: A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010-2012 followed by an apparent decline during 2013-2017. However, the activities of CVA16 increased gradually during 2018-2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10-3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. CONCLUSIONS: The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010-2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.
Assuntos
Enterovirus , Doença de Mão, Pé e Boca , Pequim/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Enterovirus/genética , Doença de Mão, Pé e Boca/diagnóstico , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Epidemiologia Molecular , FilogeniaRESUMO
Anti-washout CaF(2) stabilized C(3)S (F-C(3)S) bone cement was prepared by adding water-soluble carboxymethyl chitosan (CMCS) to the hydration liquid. The setting time, compressive strength and in vitro bioactivity of the CMCS modified F-C(3)S (CMCS-C(3)S) pastes were evaluated. The results indicate that CMCS-C(3)S pastes could be stable in the shaking simulated body fluid (SBF) after immediately mixed. The addition of CMCS significantly enhances the cohesion of particles, at the same time restrains the penetration of liquid, and thus endows the anti-washout ability. The setting times of the pastes increase with the increase of CMCS concentrations in the hydration liquid. Besides, the compressive strengths of CMCS-C(3)S pastes after setting for 1-28 days are lower than that of the pure F-C(3)S paste, but the sufficient strengths would be suitable for the clinical applications. The crystalline apatite deposited on the paste surface is retarded from 1 to 2 days for the addition of CMCS, but the quantities of deposited apatite are same after soaking in SBF for 3 days. As the result that pure C(3)S paste has shorter setting times than pure F-C(3)S paste, CMCS modified pure C(3)S pastes would have better anti-washout ability. Our study provides a convenient way to use C(3)S bone cement with excellent anti-washout ability when the pastes are exposed to biological fluids. The novel anti-washout CMCS-C(3)S bone cement with suitable setting times, sufficient strengths and in vitro bioactivity would have good prospects for medical application.
Assuntos
Cimentos Ósseos/química , Cimentos Ósseos/síntese química , Compostos de Cálcio/química , Quitosana/análogos & derivados , Silicatos/química , Fenômenos Biomecânicos/fisiologia , Líquidos Corporais/química , Líquidos Corporais/fisiologia , Compostos de Cálcio/síntese química , Células Cultivadas , Cimentação , Quitosana/síntese química , Quitosana/química , Força Compressiva/fisiologia , Teste de Materiais , Microscopia Eletrônica de Varredura , Pós/química , Silicatos/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios XRESUMO
Liposome is a traditional drug-delivery system and most novel studies have focused on its drug release function. In this paper, a new drug-delivery system based on liposomes was prepared, which contains hydrophobic FeAg alloy nanoparticles (FeAgNPs) in their lipid bilayer and berberine as test drug in their middle water phase. The size of AgFe-Ls was about 200 nm, the encapsulation efficiency of drugs was 35% and the lower critical solution temperature (LCST) of AgFe-Ls was about 41.96 °C. FeAgNPs in the AgFe-Ls had a 1:1 iron-to-silver atomic ratio with both optical and superparamagnetic properties. The photothermal effect and magnetocaloric effect of FeAgNPs could serve up both photo-stimulated and magnetic- stimulated drug release to liposomes. Release experiments results showed that AgFe-Ls could easily release berberine when stimulated by UV light (45% drug release at 20 min) or alternating current electromagnetic field (AMF) (80% drug release at 4 h). AgFe-Ls with both photo-controlled and magnetic-controlled drug release functions are promising to serve up chemotherapy drugs to cancer cells.
Assuntos
Nanopartículas , Neoplasias , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Lipossomos , Fenômenos Magnéticos , Neoplasias/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. AIM OF THE STUDY: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. MATERIALS AND METHODS: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549â¯cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. RESULTS: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-κB activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. CONCLUSIONS: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-κB centered inflammation-cancer feedback loop. Imperialine mediated anti-cancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.
Assuntos
Alcaloides/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cevanas/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Fritillaria/química , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Alcaloides/efeitos adversos , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Contagem de Células Sanguíneas , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cevanas/efeitos adversos , Cevanas/química , Cevanas/isolamento & purificação , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Retroalimentação Fisiológica/efeitos dos fármacos , Humanos , Lipossomos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Testes de Toxicidade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Malignant melanoma, a highly dangerous type of skin cancer, is usually resistant to pro-apoptosis agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due to low death receptor expression levels. After verifying combination of chemotherapy drug paclitaxel (PTX) and TRAIL could significantly enhance their anti-melanoma effects, we developed a liposomal melanoma target-delivery system with tumor microenvironment responsiveness (TRAIL-[Lip-PTX]C18-TR) to co-deliver TRAIL and PTX. TRAIL is attached to negatively-charged liposome surface while PTX is encapsulated inside, with final surface modification of a stearyl chain (C18) fused pH-sensitive cell-penetrating peptide (TR). Here, C18-TR could specifically binds to melanoma-rich integrin receptors αvß3 for melanoma targeting, help release TRAIL in low pH microenvironment by reversing the liposomal charge, and facilitate consequent liposome internalization. TRAIL-[Lip-PTX]C18-TR displayed significantly better in vitro half-maximal inhibitory concentration (IC50) than other formulations, and an in vivo tumor inhibition rate of 93.8%. Mechanistic study revealed that this synergistic effect is associated with the upregulation of death receptors DR4/5 by PTX. This co-delivery system significantly improved TRAIL-based therapy against melanoma, and provided a simple platform to co-deliver other drugs/agents for melanoma treatment.