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1.
J Nanobiotechnology ; 22(1): 273, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773507

RESUMO

BACKGROUND: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Animais , Infecções por Acinetobacter/prevenção & controle , Camundongos , Feminino , Camundongos Endogâmicos BALB C , Vacinas Bacterianas/imunologia , Imunização , Vesículas Extracelulares , Membrana Externa Bacteriana/metabolismo , Proteínas da Membrana Bacteriana Externa/imunologia , Modelos Animais de Doenças , Humanos , Administração Intranasal , Proteínas Virais
2.
J Mater Chem B ; 11(8): 1798-1807, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36727624

RESUMO

Combined chemotherapy plays an increasingly important and practical role in the clinical treatment of malignant tumor. In this study, paclitaxel (PTX) and curcumin (Cur) are simultaneously encapsulated into nanogels (termed as NG-PC) in situ by microemulsion photopolymerization at 532 nm for synergistically suppressing breast tumors. NG-PC with a size of 180 nm and a low polydispersity index (PDI < 0.2) presents a controlled and cumulative release of PTX and Cur within 90 h. Moreover, NG-PC displays a remarkable killing effect against 4T1 and MCF-7 cells. In vivo antitumor evaluation on 4T1 tumor-bearing mice demonstrates that NG-PC has significantly higher ability to inhibit tumor growth, inducing necrosis, apoptosis and suppression of proliferation than that of a single drug. Our research provides a facile method to prepare a nano-drug delivery platform with excellent drug co-loading ability and synergistic antitumor effect.


Assuntos
Neoplasias da Mama , Curcumina , Humanos , Camundongos , Animais , Feminino , Paclitaxel/farmacologia , Curcumina/farmacologia , Nanogéis , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico
3.
Colloids Surf B Biointerfaces ; 217: 112611, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35679736

RESUMO

Tumor microenvironment-responsive nanogels loading antitumor drugs can improve the chemotherapy efficiency due to their suitable size, great hydrophilicity, excellent biocompatibility, and sensitivity to specific stimulation. Herein, a simple and effective strategy of one-pot laser-induced emulsion polymerization at 532 nm was developed to prepare carmofur-loaded nanogels based on biocompatible and temperature/pH-sensitive monomers including polyethylene glycol diacrylate (PEGDA), N-vinylcaprolactam (NVCL), and 2-(dimethylamino) ethyl methacrylate (DMAEMA). The nanogels loading carmofur with dual-stimuli responsive drug release properties were rapidly obtained under laser irradiation (beam diameter 2.5 mm, laser power 60 mW) for only 100 s. These nanogels exhibited an average hydrodynamic diameter of 195.9 nm and a low polydispersity index of 0.115. The effect of monomer ratio on the size, morphology, double-bond conversion, and thermo/pH-sensitivity of nanogels was investigated. The cumulative carmofur release from nanogels at pH 5.0 within 48 h was nearly three times that at pH 7.4, while the release amount at 42 °C was twice that at 25 °C, showing the controlled and sustainable release with the change of pH and temperature. The in vitro release kinetics of carmofur was in accord with first-order release model.


Assuntos
Fluoruracila , Lasers , Portadores de Fármacos/química , Emulsões , Fluoruracila/análogos & derivados , Concentração de Íons de Hidrogênio , Nanogéis , Polimerização , Temperatura
4.
Front Bioeng Biotechnol ; 9: 771851, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746113

RESUMO

In recent years, the exploration of tumor microenvironment has provided a new approach for tumor treatment. More and more researches are devoted to designing tumor microenvironment-responsive nanogels loaded with therapeutic drugs. Compared with other drug carriers, nanogel has shown great potential in improving the effect of chemotherapy, which is attributed to its stable size, superior hydrophilicity, excellent biocompatibility, and responsiveness to specific environment. This review primarily summarizes the common preparation techniques of nanogels (such as free radical polymerization, covalent cross-linking, and physical self-assembly) and loading ways of drug in nanogels (including physical encapsulation and chemical coupling) as well as the controlled drug release behaviors. Furthermore, the difficulties and prospects of nanogels as drug carriers are also briefly described.

5.
Int J Mol Med ; 44(3): 903-912, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31524225

RESUMO

Silicon is one of the most widely used chemical materials, and the increasing use of silica nanoparticles (SNs) highlights the requirement for safety and biological toxicity studies. The damaging and adverse effects of SNs on human hepatocytes remain largely unknown, as do the mechanisms involved. In the present study, the mechanisms underlying SN­induced toxicity in the human hepatocyte cell line HL­7702 were investigated. An MTT assay revealed that following exposure to SNs in the concentration range of 25­200 µg/ml, the viability of HL­7702 cells decreased, and the viability decreased further with increasing exposure time. SNs induced a delay in the S and G2/M phases of the cell cycle, and also induced DNA damage in these cells. Western blot and flow cytometry analyses revealed that cell death was mediated by mitochondrial damage and the upregulated expression of a number of pro­apoptotic proteins. In conclusion, exposure to SNs led to mitochondrial and DNA damage, resulting in apoptosis­mediated HL­7702 cell death. The study provided evidence for the cellular toxicity of SNs, and added to the growing body of evidence regarding the potential damaging effects of nanoparticles, indicating that caution should be exercised in their widespread usage.


Assuntos
Apoptose , Hepatócitos/metabolismo , Nanopartículas , Dióxido de Silício , Biomarcadores , Ciclo Celular , Linhagem Celular , Sobrevivência Celular , Dano ao DNA , Metaloproteinases da Matriz/metabolismo , Nanopartículas/efeitos adversos , Nanopartículas/química , Dióxido de Silício/química
6.
Stem Cell Res Ther ; 9(1): 311, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30428918

RESUMO

BACKGROUND: Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. Previous studies have shown that early intervention with bone marrow mesenchymal stem/stromal cells (BMSCs) has positive effect on anti-pulmonary fibrosis caused by silica dust. However, early intervention using BMSCs is not practical, and the therapeutic effects of BMSCs advanced intervention on pulmonary fibrosis have rarely been reported. In this study, we investigated the effects of advanced transplantation (on the 28th day after exposure to silica suspension) of BMSCs on an established rat model of pulmonary fibrosis. METHODS: Sprague Dawley (SD) rats were randomly divided into four groups including (1) control group (n = 6) which were normally fed, (2) silica model group (n = 6) which were exposed to silica suspension (1 mL of 50 mg/mL/rat), (3) BMSC transplantation group (n = 6) which received 1 mL BMSC suspension (2 × 106 cells/mL) by tail vein injection on the 28th day after exposure to silica suspension, and (4) BMSC-CM (conditioned medium) transplantation group (n = 6) which received CM from the same cell number by tail vein injection on the 28th day after exposure to silica suspension. On the 56th day after exposure to silica suspension, we used computed tomography (CT), hematoxylin and eosin (H&E), and Masson's trichrome staining to evaluate the changes in lung tissue. We examined the expression of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related proteins in lung tissue using immunohistochemistry and western blotting. RESULTS: Successful construction of a pulmonary fibrosis model was confirmed by H&E and Masson's trichrome staining on the 28th day after exposure to silica suspension. On the 56th day after exposure, pulmonary CT examination showed a relieving effect of BMSCs on silica-induced pulmonary fibrosis which was confirmed by H&E and Masson's trichrome staining. Treatment of BMSCs increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including Vimentin (Vim) and α-Smooth actin (α-SMA) after exposure to silica suspension. Furthermore, we found that Wnt/ß-catenin signaling pathway is abnormally activated in silica-induced pulmonary fibrosis, and exogenous transplantation of BMSCs may attenuate their expression. CONCLUSIONS: BMSC transplantation inhibits the EMT to alleviate silica-induced pulmonary fibrosis in rats and the anti-fibrotic effect potentially by attenuating Wnt/ß-catenin signaling. ᅟ: ᅟ.


Assuntos
Células da Medula Óssea/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Via de Sinalização Wnt , Animais , Proliferação de Células , Ciclina D1/metabolismo , Transição Epitelial-Mesenquimal , Glicogênio Sintase Quinase 3 beta/metabolismo , Hidroxiprolina/metabolismo , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Fosforilação , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Ratos Sprague-Dawley , Dióxido de Silício , Suspensões , Tomografia Computadorizada por Raios X , beta Catenina/metabolismo
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