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2.
J Chromatogr A ; : 460741, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31810620

RESUMO

In this work, we introduced an aptamer modified Au nanoparticles doped covalent organic frameworks composite (IBAs-AuNPs/COF) to improve the property of selective enrichment of insulin from serum samples. The Au nanoparticles were immobilized on imine-based COF by in-situ reduction reaction via mussel inspired polydopamine coating, and then sulfhydryl-containing aptamers were bonded to the surface of AuNPs through an Au-S linkage. Due to the excellent adsorption property of COF and specific recognition between insulin and IBAs, the IBAs-AuNPs/COF composites show selective and satisfactory extraction property to insulin in serum samples. Excellent specifity was obtained for insulin in the presence of 50-fold interfering substances including human immunoglobulin, lysozyme and biotin. The concentrations of insulin in the range of 1.0 to 50.0 µg L-1 show good linear relationship (R2 = 0.9917) with limit of detection and limit of quantitation of 0.28 µg L-1 and 0.93 µg L-1, respectively. Then, the IBAs-AuNPs/COF composites were applied to enrich insulin in serum samples followed by analysis with matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). After the recovery experiment, the developed method shows good recoveries in range of 91.6%-112.4% with low RSD value (2.4%-9.4%, n = 3) for diabetic and healthy serum samples. The developed IBAs-AuNPs/COF composites propose a new perspective for selective and efficient enrichment of biomarkers in serum samples by functionalized COF.

3.
Front Pharmacol ; 10: 842, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402868

RESUMO

Ursodeoxycholic acid (UDCA) is a bile acid (BA) approved by the U.S. Food and Drug Administration for the treatment of primary biliary cholangitis. It is also the major active component of bear bile used in traditional Chinese medicine to reduce fever, remove toxins, and treat liver and eye ailments. In addition, UDCA and its conjugated form have been evaluated for their potential to improve symptoms of metabolic diseases, but the results have been inconclusive. To address this issue, in this study, we investigated the effects of orally administered UDCA on mice with diet-induced obesity, including the BA and free fatty acid (FFA) profiles of serum, liver, and epididymis and brown adipose tissues. We found that UDCA treatment significantly improved most metabolic indices; tauroursodeoxycholic acid (TUDCA) and taurolithocholic acid (TLCA) contents were increased in all examined tissues, whereas saturated FA levels were decreased, and n-3 polyunsaturated fatty acid (n-3 PUFA) levels were increased in most tissues. A correlation analysis showed that the concentrations of UDCA and its derivatives were positively correlated with that of n-3 PUFA. To clarify the mechanism by which UDCA alters FFA profiles, we analyzed the expression levels of genes involved in FFA biosynthesis, uptake, and oxidation and found that FFA biosynthesis and uptake were inhibited while FFA oxidation was stimulated by UDCA treatment. Additionally, amino acid-conjugated derivatives of UDCA, such as TUDCA and TLCA, altered FFA profiles by modulating FFA biosynthesis, uptake, and oxidation. These findings provide evidence that UDCA can alleviate metabolic dysfunction and could therefore be effective in the treatment of obesity.

4.
ACS Nano ; 13(7): 7556-7567, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31259530

RESUMO

Bone metastasis, a clinical complication of patients with advanced breast cancer, seriously reduces the quality of life. To avoid destruction of the bone matrix, current treatments focus on inhibiting the cancer cell growth and the osteoclast activity through combination therapy. Therefore, it could be beneficial to develop a bone-targeted drug delivery system to treat bone metastasis. Here, a bone-targeted nanoplatform was developed using gold nanorods enclosed inside mesoporous silica nanoparticles (Au@MSNs) which were then conjugated with zoledronic acid (ZOL). The nanoparticles (Au@MSNs-ZOL) not only showed bone-targeting ability in vivo but also inhibited the formation of osteoclast-like cells and promoted osteoblast differentiation in vitro. The combination of Au@MSNs-ZOL and photothermal therapy (PTT), triggered by near-infrared irradiation, inhibited tumor growth both in vitro and in vivo and relieved pain and bone resorption in vivo by inducing apoptosis in cancer cells and improving the bone microenvironment. This single nanoplatform combines ZOL and PTT to provide an exciting strategy for treating breast cancer bone metastasis.

5.
Mikrochim Acta ; 186(3): 197, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30796600

RESUMO

Near infrared (NIR)-emitting persistent luminescent nanoparticles (PLNPs) have advantages such as long afterglow, high photostability and deep tissue spectral penetration. A NIR-emitting inner filter effect (IFE) probe for arsenic(III) is described here. It is composed of polyethyleneimine-coated PLNPs and gold nanorods (AuNPs) coated with dithiothreitol. The probe can detect arsenic(III) (= arsenite) selectively even in the presence of interfering substances. The PLNPs and AuNPs were prepared by a hydrothermal method combined with high-temperature calcination and seed-mediated growth mechanism, respectively. The PLNPs show excellent NIR luminescence (with excitation/emission peaks at 254/695 nm) and long afterglow (lifetime >1200 s). The use of polyethyleneimine improves water solubility and provides positive surface charges for the PLNPs. On exposure to arsenite ions, the luminescence of the probe at 695 nm is restored. Under the optimum conditions, the method can detect As(III) in the 0.067 to 13.4 µmol·L-1 concentration range with good linear relationship (R2 = 0.99734), and the detection limit (at S/N = 3) is 55 nmol·L-1. The precision of this method was demonstrated by 11 replicate detections of 2 µmol·L-1 As(III), and the relative standard deviations (RSD) is 2.1%. The practicality was evaluated by the analyses of real water samples and recoveries for the water samples spiked with 2, 5 and 10 µmol·L-1 of As(III) were 89.8%-100.1% with RSDs ranging from 3.0-5.7%. Graphical abstract A near infrared-emitting inner filter effect (IFE) inhibition probe is presented. It is based on the combination of polyethyleneimine (PEI)-coated NIR-emitting persistent luminescent nanoparticles (type Zn1.25Ga1.5Ge0.25O4: Cr3+, ZGGO) (PLNPs-PEI) with dithiothreitol (DTT)-coated gold nanorods (AuNPs) (DTT-AuNPs) to detect arsenite.

6.
Front Pharmacol ; 10: 63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804786

RESUMO

Pu-erh tea has been extensively reported to possess lipid lowering effects but the underlying mechanisms remained unclear. Free fatty acids (FFAs) are generally correlated with the development of obesity, leading to increased risk for type 2 diabetes mellitus and cardiovascular diseases. To investigate whether Pu-erh tea treatment alters FA metabolism, we treated HFD induced obese mice with Pu-erh tea for 22 weeks and analyzed FFA profiles of experimental mice using a UPLC-QTOF-MS platform. Results showed remarkable changes in metabolic phenotypes and FFA compositions in mice treated with or without Pu-erh tea. HFD induced a marked obese phenotype in mice as revealed by significantly increased body weight, liver and adipose tissue weight, lipid levels in serum and liver, and these parameters were markedly reduced by Pu-erh tea treatment. Several FFA or FFA ratios, such as DGLA, palmitoleic acid, and OA/SA ratio, were significantly increased while the levels of SA/PA and AA/DGLA were significantly reduced in HFD-induced obese mice. Interestingly, these differential FFAs or FFA ratios were previous identified as key markers in human obese subjects, and their changes observed in the HFD group were reversed by Pu-erh tea treatment. Moreover, a panel of FFA markers including C20:3 n6/C18:3 n6 and C20:3 n6/C20:2 n6, C18:3 n6/C18:2 n6, C18:3 n3/C18:2 n6 and C24:1 n9/C22:1 n9, which were previously identified as biomarkers in predicting the remission of obesity and diabetes in human subjects who underwent metabolic surgery procedures, were reversed by Pu-erh tea intervention. Pu-erh tea significantly improved glucose homeostasis and insulin tolerance compared to the HFD group. Additionally, Pu-erh tea treatment significantly decreased FFA synthesis genes and increased the expression of genes involved in FFA uptake and ß-oxidation including FATP2, FATP5, PPARα, CPT1α, and ACOX-1. These finding confirmed the beneficial effects of Pu-erh tea on regulating lipid and glucose metabolism, and further validated a panel of FFA markers with diagnostic and prognostic value for obesity and diabetes.

7.
ACS Nano ; 13(1): 313-323, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30571089

RESUMO

Y2O3 nanoparticles (NPs) have become great promising products for numerous applications in nanoscience especially for biomedical application, therefore increasing the probability of human exposure and gaining wide attention in biosecurity. It is well known that rare earth (RE) materials are deposited in the bone and excreted very slowly. Nevertheless, the effect of Y2O3-based NPs on bone metabolism has not been exactly known yet. In the present study, the effects of Y2O3 NPs on bone marrow stromal cells (BMSCs) and bone metabolism in mice after intravenous injection were studied. The results demonstrated that Y2O3 NPs could be taken up into BMSCs and localized in acidifying intracellular lysosomes and underwent dissolution and transformation from Y2O3 to YPO4, which could lead to a break in the intracellular phosphate balance and induce lysosomal- and mitochondrial-dependent apoptosis pathways. Furthermore, after being administered to mice, a higher concentration of yttrium occurred in bone, which caused the apoptosis of bone cells and induced the destruction of bone structure. However, the formation of a YPO4 coating on the surface of Y2O3 NPs by pretreatment of Y2O3 NPs in lysosome-simulated body fluid could observably decrease the toxicity in vivo and in vitro. This study may be useful for practical application of Y2O3 NPs in the biomedical field.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Nanopartículas/toxicidade , Fosfatos/metabolismo , Ítrio/toxicidade , Animais , Apoptose , Células da Medula Óssea/metabolismo , Catepsinas/metabolismo , Células Cultivadas , Feminino , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/genética , Mitocôndrias/metabolismo , Nanopartículas/química , Ítrio/química , Ítrio/farmacocinética
8.
Int J Biol Macromol ; 118(Pt B): 1550-1557, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29981327

RESUMO

In order to improve the bioactivity of the polysaccharide from Sargassum fusiforme (PSF), the degraded polysaccharide (DPSF) was modified by carboxymethylation, yielding carboxymethylated degraded polysaccharides (CDPSF), which were further modified to generate hydroxamated derivatives (HCDPSF). Both CDPSF and HCDPSF were characterized by Fourier transform infrared spectroscopy. The molecular weight of CDPSF and HCDPSF was found to be 354 kDa and 375 kDa, respectively. The in vitro antioxidant activity of CDPSF and HCDPSF was evaluated by determining the radical scavenging ability and total antioxidant activity. The results indicated that the antioxidant activity of CDPSF and HCDPSF was significantly improved when compared to those of DPSF. Antimicrobial assays indicated that both CDPSF and HCDPSF possessed a marked antimicrobial ability, while DPSF did not exhibit such effects under the same conditions. Such polysaccharide derivatives have potentials in the pharmaceutical and food industries.


Assuntos
Ácidos Hidroxâmicos/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Radicais Livres/química , Metilação , Testes de Sensibilidade Microbiana , Peso Molecular
9.
Sensors (Basel) ; 18(7)2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30037086

RESUMO

A colorimetric probe for determination of As(III) ions in aqueous solutions on basis of localized surface plasmon resonance (LSPR) was synthesized. The dithiothreitol molecules with two end thiols covalently combined with Au Nanorods (AuNRs) with an aspect ratio of 2.9 by Au-S bond to form dithiothreitol coated Au Nanorods (DTT-AuNRs), acting as colorimetric probe for the determination of As(III) ions. With the adding of As(III) ions, the AuNRs will be aggregated and leading the longitudinal SPR absorption band of DTT-AuNRs decrease due to the As(III) ions can bind with three DTT molecules through an As-S linkage. The potential factors affect the response of DTT-AuNRs to As(III) ions including the concentration of DTT, pH values of DTT-AuNRs, reaction time and NaCl concentration were optimized. Under optimum assay conditions, the DTT-AuNRs colorimetric probe has high sensitivity towards As(III) ions with low detection limit of 38 nM by rules of 3σ/k and excellent linear range of 0.13⁻10.01 µM. The developed colorimetric probe shows high selectivity for As(III) ions sensing and has applied to determine of As(III) in environmental water samples with quantitative spike-recoveries range from 95.2% to 100.4% with low relative standard deviation of less than 4.4% (n = 3).

10.
FASEB J ; 32(9): 4878-4888, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29620942

RESUMO

Food withdrawal as a health-enhancing measure has beneficial effects on aging, disease prevention, and treatment. However, the cellular and molecular mechanisms involving gut microbial changes and metabolic consequences resulting from food withdrawal have yet to be elucidated. In this study, we subjected lean and obese mice to a dietary intervention that consisted of a 4-d complete food withdrawal and an 8-d 50% food withdrawal, and we studied changes in cecal microbiome and host serum metabolome. The abundance of potentially pathogenic Proteobacteria was decreased and Akkermansia muciniphila was elevated by food withdrawal in mice fed a high-fat diet (HFD). Meanwhile, food withdrawal decreased the abundance of metabolites in branched chain amino acid, lipid, and free fatty acid metabolisms in host serum, more so in HFD mice than in normal mice. Microbial predicted function also showed that food withdrawal decreased the abundance of microbes associated with predicted diseases in the HFD group but not in the normal chow group. Correlation between the microbiome data and metabolomics data revealed a strong association between gut microbial and host metabolic changes in response to food withdrawal. In summary, our results showed that food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and the beneficial effects were primarily derived from the changes in gut microbiota, which were closely associated with the host metabolome.-Zheng, X., Zhou, K., Zhang, Y., Han, X., Zhao, A., Liu, J., Qu, C., Ge, K., Huang, F., Hernandez, B., Yu, H., Panee, J., Chen, T., Jia, W., Jia, W. Food withdrawal alters the gut microbiota and metabolome in mice.


Assuntos
Alimentos , Microbioma Gastrointestinal/fisiologia , Metaboloma/fisiologia , Microbiota/fisiologia , Animais , Dieta Hiperlipídica , Metabolismo dos Lipídeos/fisiologia , Metabolômica/métodos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
11.
Int J Nanomedicine ; 13: 1707-1721, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29599615

RESUMO

Introduction: poly(l-lactic acid) (PLLA) has been approved for clinical use by the US Food and Drug Administration (FDA); however, their stronger hydrophobicity and relatively fast degradation rate restricted their widespread application. In consideration of the composition of bone, the inorganic-organic composite has a great application prospect in bone tissue engineering. Many inorganic-organic composite scaffolds were prepared by directly mixing the active ingredient, but this method is uncontrolled and will lead to lack of homogeneity in the polymer matrix. Strontium (Sr) is an admirable addition to improve the bioactivity and bone induction of hydroxyapatite (HA). To our knowledge, the application of biomimetic mineralized strontium-doped hydroxyapatite on porous poly(l-lactic acid) (Sr-HA/PLLA) scaffolds for bone defect repair has never been reported till date. Biomimetic mineralized Sr-HA/PLLA porous scaffold was developed in this study. The results indicated that the Sr-HA/PLLA porous scaffold could improve the surface hydrophobicity, reduce the acidic environment of the degradation, and enhance the osteoinductivity; moreover, the ability of protein adsorption and the modulus of compression were increased. The results also clearly showed the effectiveness of the Sr-HA/PLLA porous scaffold in promoting cell adhesion, proliferation, and alkaline phosphatase (ALP) activity. The micro computed tomography (micro-CT) results showed that more new bones were formed by Sr-HA/PLLA porous scaffold treatment. The histological results confirmed the osteoinductivity of the Sr-HA/PLLA porous scaffold. The results suggested that the Sr-HA/PLLA porous scaffold has a good application prospect in bone tissue engineering in the future. Purpose: The purpose of this study was to promote the bone repair. Materials and methods: Surgical operation of rabbits was carried out in this study. Results: The results showed that formation of a large number of new bones by the Sr-HA/PLLA porous scaffold treatment is possible. Conclusion: Biomimetic mineralized Sr-HA/PLLA porous scaffold could effectively promote the restoration of bone defects in vivo.


Assuntos
Biomimética/métodos , Hidroxiapatitas/química , Poliésteres/química , Estrôncio/química , Tecidos Suporte/química , Animais , Regeneração Óssea , Osso e Ossos , Calcificação Fisiológica/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Poliésteres/farmacologia , Porosidade , Coelhos , Engenharia Tecidual/métodos , Microtomografia por Raio-X
12.
J Agric Food Chem ; 65(37): 8229-8240, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28837320

RESUMO

Probiotics has attracted great attention in food nutrition and safety research field, but thus far there are limited analytical techniques for visualized and real-time monitoring of the probiotics when they are ingested in vivo. Herein, the optical bioimaging technique has been introduced for investigation of foodborne probiotics biodistribution in vivo, employing the near-infrared (NIR) emitting persistent luminescence nanophosphors (PLNPs) of Cr3+-doped zinc gallogermanate (ZGGO) as the contrast nanoprobes. The ultrabrightness, super long afterglow, polydispersed size, low toxicity, and excellent photostability and biocompatibility of PLNPs were demonstrated to be qualified as a tracer for labeling probiotics via antibody (anti-Gram positive bacteria LTA antibody) recognition as well as contrast agent for long-term bioimaging the probiotics. In vivo optical bioimaging assay showed that the LTA antibody functionalized ZGGO nanoprobes that could be efficiently tagged to the probiobics were successfully applied for real-time monitoring and nondamaged probing of the biodistribution of probiotics inside the living body after oral administration. This work presents a proof-of-concept that exploited the bioimaging methodology for real-time and nondamaged researching the foodborne probiotics behaviors in vivo, which would open up a novel way of food safety detection and nutrition investigation.


Assuntos
Lactobacillus reuteri/química , Nanopartículas/química , Probióticos/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Imagem Corporal Total/métodos , Animais , Linhagem Celular , Feminino , Humanos , Luminescência , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Tecidual
13.
J Phys Chem Lett ; 8(17): 3986-3990, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28797165

RESUMO

A polymeric ionic liquid (PIL), with quaternary ammonium ions attached to the polymer matrix, displays CO2 affinity controlled by moisture. This finding led to the development of moisture swing absorption (MSA) for direct air capture of CO2. This work aims to elucidate the role of water in MSA. For some humidity range, CO2 absorption is an endothermic process associated with concurrent dehydration of the sorbent. The thermodynamic behavior of water indicates a decreased hydrophilicity of the PIL as the mobile anion transforms from CO32- to HCO3- during CO2 absorption. The decrease in hydrophilicity drives water out of the PIL, carrying heat away. The mechanism is elucidated by molecular modeling based on density functional theory. The finding of spontaneous cooling during absorption and its mechanism in the PIL opens new possibilities for designing an air capture sorbent with a strong CO2 affinity but low absorption heat.

14.
Sci Rep ; 7: 45232, 2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28345673

RESUMO

Emerging evidence points to a strong association between sex and gut microbiota, bile acids (BAs), and gastrointestinal cancers. Here, we investigated the mechanistic link between microbiota and hepatocellular carcinogenesis using a streptozotocin-high fat diet (STZ-HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) murine model and compared results for both sexes. STZ-HFD feeding induced a much higher incidence of HCC in male mice with substantially increased intrahepatic retention of hydrophobic BAs and decreased hepatic expression of tumor-suppressive microRNAs. Metagenomic analysis showed differences in gut microbiota involved in BA metabolism between normal male and female mice, and such differences were amplified when mice of both sexes were exposed to STZ-HFD. Treating STZ-HFD male mice with 2% cholestyramine led to significant improvement of hepatic BA retention, tumor-suppressive microRNA expressions, microbial gut communities, and prevention of HCC. Additionally the sex-dependent differences in BA profiles in the murine model can be correlated to the differential BA profiles between men and women during the development of HCC. These results uncover distinct male and female profiles for gut microbiota, BAs, and microRNAs that may contribute to sex-based disparity in liver carcinogenesis, and suggest new possibilities for preventing and controlling human obesity-related gastrointestinal cancers that often exhibit sex differences.


Assuntos
Bactérias/classificação , Carcinoma Hepatocelular/microbiologia , Dieta Hiperlipídica/efeitos adversos , Neoplasias Hepáticas/microbiologia , Metagenômica/métodos , Hepatopatia Gordurosa não Alcoólica/microbiologia , Estreptozocina/efeitos adversos , Animais , Ácidos e Sais Biliares/metabolismo , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Resina de Colestiramina/farmacologia , Resina de Colestiramina/uso terapêutico , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Incidência , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Masculino , Camundongos , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fatores Sexuais
15.
ACS Appl Mater Interfaces ; 9(7): 5784-5792, 2017 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-28118705

RESUMO

Europium-doped Gd2O3 nanotubes (Gd2O3:Eu3+ NTs) have been extensively applied in the field of bioscience for their photostability and magnetic properties. Nevertheless, the distribution and interaction between Gd2O3:Eu3+ NTs and metabolism of bone are not yet sufficiently understood. In this study, a systematic study of the toxicity and distribution of Gd2O3:Eu3+ NTs in mice after oral administration was carried out. The results showed that a small number of the Gd2O3:Eu3+ NTs could pass through biological barriers into the lung, liver, and spleen, but a high concentration was observed in bone. Furthermore, the effects of Gd2O3:Eu3+ NTs on bone metabolism were systematically studied in vitro and in vivo when accumulating in bone. After being administered to mice, the Gd2O3:Eu3+ NTs extremely enhanced the bone mineral density and bone biomechanics. In vitro the Gd2O3:Eu3+ NTs increased the alkaline phosphatase (ALP) activity and mineralization and promoted the expression of osteogenesis genes in preosteoblasts MC3T3-E1 through activation of the BMP signaling pathway. This study will be significant for appropriate application of Gd2O3:Eu3+ NTs in the biomedical field and expounding the molecular mechanism of bone metabolism.


Assuntos
Nanotubos , Animais , Densidade Óssea , Európio , Gadolínio , Camundongos , Osteoblastos , Osteogênese , Transdução de Sinais
16.
Biomaterials ; 122: 23-33, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28107662

RESUMO

Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8+ cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm. TAAs can be loaded into MOFs in the one-pot synthesis process and released with the degradation of MOFs in the acidic environment of endo/lysosome as the result of relatively labile metal-ligand bonds. The endosomolytic nanoparticles would facilitate protein antigens escape from endo/lysosome and optimal for enhancing antigen cross-presentation. Furthermore, the introduction of immunostimulatory unmethylated cytosine-phosphate-guanine oligonucleotide (CpG) through Watson-Crick base pairing would further enhance CD8+ cytotoxic T lymphocyte responses. We demonstrated that the method to co-delivery antigens and immunostimulatory molecules was very simple, convenient and effective and showed no obvious toxicity both in vitro and in vivo. This method gave a high antigens-loading capacity and the maximal antigen encapsulating efficiency was about 55% (w/w). Additionally, the pH-responsive co-delivery system exerted enhanced antitumor outcome (about 100% survival) in B16-OVA melanoma cancers in vivo. Furthermore, we confirmed that this high rating of therapeutic effect was attributed to the recruitment of tumor-killing immunocyte. This work demonstrates the ability of pH-responsive, endosomolytic MOFs to induce strong cellular immune responses for cancer therapy by co-delivery of CpG ODN and antigens.


Assuntos
Antígenos de Neoplasias/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Estruturas Metalorgânicas/síntese química , Nanocápsulas/química , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linhagem Celular Tumoral , Sinergismo Farmacológico , Concentração de Íons de Hidrogênio , Estruturas Metalorgânicas/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Células RAW 264.7
17.
J Nanosci Nanotechnol ; 17(1): 153-60, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29617096

RESUMO

Monodisperse mesoporous silica nanospheres with novel self-activated luminescence have been fabricated by a modified templating sol­gel method followed by heat treatment, without introducing any rare earth or transition metal ions as activators. The SEM, TEM, and N2 adsorption/desorption isotherms results show that the as-obtained mesoporous silica nanospheres exhibit well-defined morphology, good dispersion, high specific surface area and pore volume. MTT assay indicates that the sample exhibits no obvious cytotoxicity against the A549, HeLa, and MCF-7 cells, which make it suitable to be utilized as a drug carrier. Under ultraviolet excitation, the sample exhibits an intense blue emission. Interestingly, the photoluminescence intensity of the IBU drug loaded system increases with the increase of cumulatively released IBU. Due to the relationship between the luminescence properties and drug release behavior, the as-obtained luminescent drug carrier may be potential as a probe for monitoring or detecting the drug release process.


Assuntos
Portadores de Fármacos/química , Substâncias Luminescentes/química , Nanosferas/química , Dióxido de Silício/química , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/toxicidade , Células HeLa , Humanos , Substâncias Luminescentes/toxicidade , Células MCF-7 , Nanosferas/toxicidade , Dióxido de Silício/toxicidade
18.
Oncol Lett ; 12(3): 2189-2193, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27602162

RESUMO

Genistein is a soybean isoflavone; in its aglycone it has various biological activities. Animal experiments, clinical studies and epidemiological investigations suggest that genistein has preventative and curative functions for a number of diseases, particularly in cancer. The present study explored the potential anti-cancer effect of genistein by observing its role in inhibiting A549 human lung cancer cell proliferation and investigating the possible mechanism. A549 cells were exposed to various concentrations of genistein (0, 10, 25, 50, 100 and 200 µM; dissolved in physiological saline) for 1, 2 and 3 days. Subsequently, the viability of A549 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined using a flow cytometer, caspase 3/9 activity was measured using commercial kits, reverse transcription quantitative polymerase chain reaction was used to analyze the miR-27a expression and western blotting was used to investigate MET protein expression. The results suggested a significant inhibition of A549 cell growth following treatment with genistein in a time- and dose-dependent manner. The current study also indicated that treatment with genistein significantly induces cell apoptosis and promotes caspase-3/9 activation of A549 cells in a dose-dependent manner. Further functional assays revealed that the anti-cancer effect of genistein activated microRNA-27a (miR-27a) expression levels and reduced MET protein expression in A549 cells. In conclusion, the present study demonstrates that genistein inhibits A549 human lung cancer cell proliferation. Furthermore, this study reports, for the first time, a correlation between the anti-cancer effect of genistein and miR-27a-mediated MET signaling.

19.
ACS Appl Mater Interfaces ; 8(38): 25078-86, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27589262

RESUMO

The rare earth hollow spheres with up-conversion luminescence properties have shown potential applications in drug delivery and bioimaging fields. However, there have been few reports for the degradation properties of rare earth oxide drug carriers. Herein, uniform and well-dispersed Y2O3:Yb(3+),Er(3+) hollow spheres (YOHSs) have been fabricated by a general Pechini sol-gel process with melamine formaldehyde colloidal spheres as template. The novel YOHSs with up-conversion luminescence has good drug loading amount and drug-release efficiency; moreover, it exhibits pH-responsive release patterns. In particular, the YOHSs sample exhibits low cytotoxicity and excellent degradable properties in acid buffer. After the sample was loaded with anticancer drug doxorubicin (DOX), the antitumor result in vitro indicates that YOHS-DOX might be effective in cancer treatment. The animal imaging test also reveals that the YOHSs drug carrier can be used as an outstanding luminescent probe for bioimaging in vivo application prospects. The results suggest that the degradable drug carrier with up-conversion luminescence may enhance the delivery efficiency of drugs and improve the cancer therapy in clinical applications.


Assuntos
Portadores de Fármacos/química , Animais , Doxorrubicina , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Érbio , Luminescência , Neoplasias , Ítrio
20.
Langmuir ; 32(36): 9237-44, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27531422

RESUMO

Once bone metastasis occurs, the chances of survival and quality of life for cancer patients decrease significantly. With the development of nanomedicine, nanocarriers loading bisphosphonates have been built to prevent cancer metastasis based on their enhanced permeability and retention (EPR) effects; however, as a passive mechanism, the EPR effects cannot apply to the metastatic sites because of their lack of leaky vasculature. In this study, we fabricated 40 nm-sized mesoporous silica nanoparticles (MSNs) anchored by zoledronic acid (ZOL) for targeting bone sites and delivered the antitumor drug doxorubicin (DOX) in a spatiotemporally controlled manner. The DOX loading and release behaviors, bone-targeting ability, cellular uptake and its mechanisms, subcellular localization, cytotoxicity, and the antimigration effect of this drug delivery system (DDS) were investigated. The results indicated that MSNs-ZOL had better bone-targeting ability compared with that of the nontargeted MSNs. The maximum loading capacity of DOX into MSNs and MSNs-ZOL was about 1671 and 1547 mg/g, with a loading efficiency of 83.56 and 77.34%, respectively. DOX@MSNs-ZOL had obvious pH-sensitive DOX release behavior. DOX@MSNs-ZOL entered into cells through an ATP-dependent pathway and then localized in the lysosome to achieve effective intracellular DOX release. The antitumor results indicated that DOX@MSNs-ZOL exhibited the best cytotoxicity against A549 cells and significantly decreased cell migration in vitro. This DDS is promising for the treatment of cancer bone metastasis in the future.


Assuntos
Neoplasias Ósseas/secundário , Difosfonatos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Imidazóis/administração & dosagem , Dióxido de Silício/química , Células A549 , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/química , Doxorrubicina/química , Humanos , Imidazóis/química , Microscopia Eletrônica de Varredura , Ácido Zoledrônico
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