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1.
Phys Chem Chem Phys ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38938214

RESUMO

The fabrication of photoelectrodes on indium tin oxide (ITO) glass at low temperatures poses a significant challenge due to the inherent instability of ITO at reduced temperatures, while the inexpensive production of high-functionality photoanode technology is a critical determinant facilitating large-scale photovoltaic conversion in water splitting. In this work, highly efficient BiVO4 (BVO) photoanodes with different thicknesses were grown on ITO glass at a low temperature by the sol-gel spin coating method. Pure BVO photoanode, enriched with nanostructures, exhibits a current density of 2.25 mA cm-2 (@1.23 V vs. RHE) under AM-1.5G illumination. The photovoltaic effect induces a continual oxygen evolution reaction at zero bias voltage on the photoanode, resulting in a photocurrent density of 0.04 mA cm-2 at zero bias. This study not only evaluates the feasibility of the large-scale fabrication of a photoanode from economic considerations but also presents potential for water splitting properties of the BVO photoanode.

2.
Crit Rev Food Sci Nutr ; 62(1): 1-12, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33261516

RESUMO

Short-chain fatty acids (SCFAs) are carboxylic acids with carbon atom numbers less than 6, which are important metabolites of gut microbiome. Existing research shows that SCFAs play a vital role in the health and disease of the host. First, SCFAs are the key energy source for colon and ileum cells, and affect the intestinal epithelial barrier and defense functions by regulating related gene expression. Second, SCFAs regulate the function of innate immune cells to participate in the immune system, such as macrophages, neutrophils and dendritic cells. Third, SCFAs can also regulate the differentiation of T cells and B cells and the antigen-specific adaptive immunity mediated by them. Besides, SCFAs are raw materials for sugar and lipid synthesis, which provides a theoretical basis for studying the potential role of SCFAs in regulating energy homeostasis and metabolism. There are also studies showing that SCFAs inhibit tumor cell proliferation and promote apoptosis. In this article, we summarized in detail the role of SCFAs in immunity, inflammation and metabolism, and briefly introduced the role of SCFAs in tumor cell survival. It provides a systematic theoretical basis for the study of SCFAs as potential drugs to promote human health.


Assuntos
Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Colo , Humanos , Sistema Imunitário , Inflamação
3.
Chem Rev ; 120(3): 1710-1787, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31899631

RESUMO

Since the positive influences of defects on the performance of electroceramics were discovered, investigations concerning on defects and aliovalent doping routes have grown rapidly in the fields of inorganic chemistry and condensed matter physics. In this article, we summarized the types of defects in electroceramics as well as characterization tools of defects and highlighted the effects of intrinsic and extrinsic defects on the material performances with the emphasis on dielectric, ferroelectric, and piezoelectric properties. We mainly introduced defect related theoretical simulation and experimental results in several typical incipient ferroelectrics, ferroelectrics, and antiferroelectrics. Hence, the influences of defects on the crystal lattice were summed up, and then the main physical mechanisms were highlighted. Particularly, the performance enhancements of aliovalently doped electroceramics were also evaluated and reviewed. Finally, the outlook and challenges were discussed on the basis of their current developments. This article covers not only an overview of the state-of-the-art advances of defects and aliovalent doping routes in electroceramics but also the future prospects that may open another window to tune the electrical performance of electroceramics via intentionally introducing certain defects.

4.
BJOG ; 129 Suppl 2: 40-49, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36485069

RESUMO

OBJECTIVE: The aim was to assess the expression levels of SLC7A11 and GPX4 in relation to platinum resistance and prognosis in patients with epithelial ovarian cancer (EOC). DESIGN: A retrospective cohort study. SETTING: Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. POPULATION OR SAMPLE: We included 192 eligible patients from hospital between January 2002 and December 2018. METHODS: We retrospectively analysed the medical records of patients with EOC. Surgical specimens of EOC were stained for SLC7A11 and GPX4. Survival analysis was performed using the Kaplan-Meier and Cox regression methods. MAIN OUTCOME MEASURES: Clinical end points include platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with high co-expression levels of SLC7A11 and GPX4 had a 60-fold higher risk of platinum resistance compared with those with low co-expression (risk ratio, 60.46; 95% confidence interval [CI] 22.76-160.58; p < 0.001). Moreover, high co-expression level of SLC7A11 and GPX4 was an independent prognostic factor for poor OS (p < 0.001, hazard ratio [HR] 4.44, 95% CI, 2.77-7.14) and poor PFS (p < 0.001, HR = 5.73, 95% CI, 3.86-8.73). For in vitro experiments, SLC7A11 and GPX4 expression were both upregulated in platinum-resistant cells compared with their parental ovarian cancer cells, and siRNA-induced SLC7A11 and GPX4 inhibition decreased platinum resistance. CONCLUSIONS: High expression levels of SLC7A11 and GPX4 are associated with platinum resistance in EOC patients. High co-expression of SLC7A11 and GPX4 may be a significant independent prognostic factor and a potential therapeutic target for platinum resistance in EOC patients.


Assuntos
Carcinoma Epitelial do Ovário , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Feminino , Humanos , Sistema y+ de Transporte de Aminoácidos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Platina/metabolismo , Platina/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo
5.
J Nanobiotechnology ; 19(1): 93, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789653

RESUMO

Metal sulfide nanomaterials (MeSNs) are a novel class of metal-containing nanomaterials composed of metal ions and sulfur compounds. During the past decade, scientists found that the MeSNs engineered by specific approaches not only had high biocompatibility but also exhibited unique physicochemical properties for cancer therapy, such as Fenton catalysis, light conversion, radiation enhancement, and immune activation. To clarify the development and promote the clinical transformation of MeSNs, the first section of this paper describes the appropriate fabrication approaches of MeSNs for medical science and analyzes the features and limitations of each approach. Secondly, we sort out the mechanisms of functional MeSNs in cancer therapy, including drug delivery, phototherapy, radiotherapy, chemodynamic therapy, gas therapy, and immunotherapy. It is worth noting that the intact MeSNs and the degradation products of MeSNs can exert different types of anti-tumor activities. Thus, MeSNs usually exhibit synergistic antitumor properties. Finally, future expectations and challenges of MeSNs in the research of translational medicine are spotlighted.


Assuntos
Nanoestruturas/química , Neoplasias/tratamento farmacológico , Sulfetos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Hipertermia Induzida , Imunoterapia , Nanopartículas/química , Nanotecnologia , Preparações Farmacêuticas , Fototerapia , Nanomedicina Teranóstica
6.
J Nanobiotechnology ; 19(1): 184, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130695

RESUMO

Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics.


Assuntos
Citarabina/uso terapêutico , Lipossomos/uso terapêutico , Metotrexato/farmacologia , Proteínas de Transporte de Nucleosídeos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose , Transportador Equilibrativo 1 de Nucleosídeo/química , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Feminino , Células Hep G2 , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Ratos Sprague-Dawley , Distribuição Tecidual
7.
AAPS PharmSciTech ; 22(1): 22, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389222

RESUMO

Novel cationic lipid-based liposomes prepared using an amphiphilic cationic lipid material, N,N-dimethyl-(N',N'-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSP), have been proposed to enhance the transfection of nucleic acids. Herein, we designed and investigated liposomes prepared using DMSP, soybean phosphatidylcholine, and cholesterol. This novel gene vector has high gene loading capabilities and excellent protection against nuclease degradation. An in vitro study showed that the liposomes had lower toxicity and superior cellular uptake and transfection efficiency compared with Lipofectamine 2000. An endosomal escape study revealed that the liposomes demonstrated high endosomal escape and released their genetic payload in the cytoplasm efficiently. Mechanistic studies indicated that the liposome/nucleic acid complexes entered cells through energy-dependent endocytosis that was mediated by fossa proteins. These results suggest that such cationic lipid-based liposome vectors have potential for clinical gene delivery.


Assuntos
Técnicas de Transferência de Genes , Lipossomos/metabolismo , Animais , Cátions , Colesterol/metabolismo , Endossomos/metabolismo , Humanos , Lipídeos/química
8.
AAPS PharmSciTech ; 21(2): 57, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912318

RESUMO

The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide-conjugated PEGylated cationic liposomes-encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Experimentais/irrigação sanguínea , Ácido Zoledrônico/administração & dosagem , Animais , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Polietilenoglicóis/química
9.
Mol Pharm ; 16(2): 786-797, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30620881

RESUMO

The poor capability of drugs to permeate through the blood-brain barrier (BBB) and further release inside glioma greatly limits the curative effects of glioma chemotherapies. In this study, we prepared angiopep-2-conjugated liposome-silica hybrid nanovehicles for targeted delivery and increased the permeation of arsenic trioxide (ATO) in glioma. Polyacrylic acid (PAA) was grafted on mesoporous silica nanoparticles (MSN) for pH-sensitive release and supporting the lipid membrane. The prepared "core-shell" nanovehicles (ANG-LP-PAA-MSN) were characterized with uniform size, high drug loading efficiency (8.19 ± 0.51%), and superior pH-sensitive release feature. From the experiments, the enhanced targeted delivery of ATO by ANG-LP-PAA-MSN (ANG-LP-PAA-MSN@ATO) was evidenced by the improvement of transport, enhanced cellular uptake, and apoptosis in vitro. In addition, the pharmacokinetic study was creatively carried out through the blood-glioma synchronous microdialysis and revealed that the half-life ( t1/2) of blood and glioma tissue in the ANG-LP-PAA-MSN@ATO treatment group was extended by 1.65 and 2.34 times compared with the ATO solution group (ATO-Sol). The targeting efficiency of ANG-LP-PAA-MSN@ATO (24.96%) was dramatically stronger than that of the ATO-Sol (5.94%). Importantly, ANG-LP-PAA-MSN@ATO had a higher accumulation (4.6 ± 2.6% ID per g) in tumor tissues and showed a better therapeutic efficacy in intracranial C6 glioma bearing rats. Taken together, the blood-glioma synchronous microdialysis was successful used for the pharmacokinetic study and real-time monitoring of drug concentrations in blood and glioma; ANG-LP-PAA-MSN could be a promising targeted drug delivery system for glioma therapy.


Assuntos
Trióxido de Arsênio/química , Trióxido de Arsênio/uso terapêutico , Portadores de Fármacos/química , Glioma/tratamento farmacológico , Nanopartículas/química , Peptídeos/química , Animais , Trióxido de Arsênio/administração & dosagem , Barreira Hematoencefálica/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glioma/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Ratos , Ratos Sprague-Dawley
10.
Phys Chem Chem Phys ; 21(29): 16359-16366, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31309950

RESUMO

Capacitors with high energy storage density, low cost, ultrafast charge-discharge capability, and environmental friendliness are in high demand for application in new energy vehicles, modern electrical systems, and high-energy laser weapons. Here, lead-free (Sr1-1.5xBix)Ti0.99Mn0.01O3 (x = 0.01, 0.05, 0.1) thin films grown on Pt/Ti/SiO2/Si substrates were obtained by a sol-gel method. All the thin films have a relatively high dielectric breakdown strength (BDS) due to the added 1% Mn and pinched polarization hysteresis loops can be observed in 5 and 10 mol% Bi-doped SrTiO3 thin films. The ferroelectric behaviors of the Bi-doped SrTiO3 thin films come from the rotation of the TiO6-octahedra induced by the formation of Bi3+-VSr dipolar defects. With the increase of doping concentration, the Pmax-Pr values of the Bi-doped SrTiO3 thin films increased dramatically and can reach 34.3 µC cm-2 upon doping with 10 mol% Bi. A high recoverable energy-storage density of 24.4 J cm-3 with excellent temperature stability was obtained for the 10 mol% Bi-doped ST thin film, which shows that the (Sr0.85Bi0.1)Ti0.99Mn0.01O3 thin film is a promising candidate for high-power energy storage applications. This finding demonstrates an improved energy density of SrTiO3-based thin film systems and a reasonable explanation for the source of the ferroelectricity based on first-principles calculations is given.

11.
AAPS PharmSciTech ; 21(1): 13, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31807947

RESUMO

The launched hepatitis B vaccine could induce powerful antibodies, whereas it failed to improve potent cellular immune responses due to that the Th2-type response-induced aluminum adjuvant was adopted. Here, to target antigen-presenting cells under the epidermis and induce potent cellular and humoral immune responses, mannose-modified poly D,L-lactide-co-glycolic acid (PLGA) was synthesized and nanoparticle (MNP)-loaded hepatitis B surface antigen (HBsAg) protein was prepared. HBsAg could be slowly released and highly presented to lymphocytes which facilitated to produce long-lasting immunity based on characters of PLGA. In vitro uptake test results showed that MNPs could enhance internalization in bone marrow-derived dendritic cells (BMDCs) and RAW 264.7 cells. Subcutaneous delivery of MNPs into mice kept humoral immune and strengthened cellular immune responses. Experimental results indicated that MNPs showed significantly modified properties compared with parental PLGA nanoparticles. Thus, the obtained MNPs could be a promising vehicle for hepatitis B vaccine delivery.


Assuntos
Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Imunização/métodos , Manose/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/métodos , Excipientes/administração & dosagem , Excipientes/química , Feminino , Antígenos de Superfície da Hepatite B/administração & dosagem , Vacinas contra Hepatite B/química , Vírus da Hepatite B/imunologia , Manose/química , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Células RAW 264.7
12.
Phys Chem Chem Phys ; 20(34): 21917-21924, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30128462

RESUMO

With the increasing demand of high energy density dielectric films, macrostructure design, for instance the construction of sandwich-structured films, has been attracting much attention due to its promise in raising the discharge energy density along with an enhanced electric breakdown strength. However, the contrast of dielectric constants between neighboring layers plays a dominate role in the distribution of the electric field, which might decrease the electric breakdown strength, and has attracted little attention up to now. Additionally, high energy storage efficiency with low energy dissipation should also be considered for dielectric applications despite enhancing the discharge energy density. In this study, the effects of dielectric constant contrast between neighboring layers have been proposed and investigated in the BiFeO3/BaTiO3/BiFeO3 sandwich-structured films through regulating the annealing temperature, in which the polarization behavior has also been tuned by partially crystallizing BiFeO3 and BaTiO3 films. As a result, the BiFeO3/BaTiO3/BiFeO3 sandwich-structured film annealed at 550 °C exhibits a favorable discharge energy density of 18.5 J cm-3 and a high energy storage efficiency of 82.3%, which result from the synergetic effect of the polarization behavior (Pm - Pr = 12.1 µC cm-2) and enhanced electric breakdown strength (EBDS = 2320 kV cm-1). By rational design of the dielectric and ferroelectric properties of individual layers, both excellent discharge energy density and energy storage efficiency could be simultaneously obtained in the sandwich-structured films.

13.
Nanotechnology ; 28(47): 475601, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-28930102

RESUMO

In order to confirm the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar+ ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar+ ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar+ ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar+ ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar+ ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar+ ion state. As for vertically oriented few-layer graphene (VFG), Ar+ ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar+ ion bombardment, and these special NCMs are promising in many fields.

14.
Analyst ; 141(14): 4495-501, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27175860

RESUMO

Neurotoxin (NT), a short-chain α-neurotoxin, is the main neurotoxic protein identified from the venom of Naja naja atra. As an effective drug for the analgesis of advanced cancer patients, NT lasts longer than morphine and does not cause addiction. However, achieving a sensitive and high-resolution measurement of NT is difficult because of the extra-low content of NT in vivo. Therefore, developing a novel method to quantify NT is essential to study its pharmacokinetics in vivo. Although NT contains four primary amine groups that could react with the thiourea in fluorescein isothiocyanate (FITC), we developed a simple and reproducible single-label fluorescent derivatization method for NT which is related to the reaction of N-terminal α-amino of NT alone under optimized derivatization conditions. Furthermore, neurotoxin labelled with fluorescein isothiocyanate (NT-FITC) was prepared by high-performance liquid chromatography (HPLC) with a purity value higher than 99.29% and identified by MALDI-TOF/TOF-MS. Finally, NT-FITC could be detected at 0.8 nmol L(-1) in rat plasma using capillary electrophoresis coupled with laser induced fluorescence detection (CE-LIF). In this paper, the established method robustly and reliably quantified NT labelled with FITC via intravenous and intramuscular administrations in vivo. In addition, this work fully demonstrated the pharmacokinetic characteristics of NT in vivo, which could reduce the risk of drug accumulation, optimize therapies, and provide sufficient evidence for the rational use of NT in clinical and research laboratories.


Assuntos
Analgésicos/análise , Proteínas Neurotóxicas de Elapídeos/análise , Eletroforese Capilar , Espectrometria de Fluorescência , Analgésicos/farmacocinética , Animais , Proteínas Neurotóxicas de Elapídeos/farmacocinética , Feminino , Fluoresceína , Fluoresceína-5-Isotiocianato/farmacocinética , Humanos , Lasers , Masculino , Espectrometria de Massas , Camundongos Endogâmicos ICR , Ratos Sprague-Dawley
15.
Yao Xue Xue Bao ; 50(7): 899-905, 2015 Jul.
Artigo em Zh | MEDLINE | ID: mdl-26552154

RESUMO

A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.


Assuntos
Canfanos/química , Dendrímeros , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Ácido Fólico/química , Transporte Biológico , Barreira Hematoencefálica , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Glioma , Humanos
16.
Phys Chem Chem Phys ; 16(26): 13078-85, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-24852079

RESUMO

BaTiO3-xAlN (BT-xAlN) composite ceramics were prepared by conventional solid state reaction sintering. The effects of the AlN content on the crystalline structures, densities, and electrical and mechanical properties of the BT ceramics were investigated. The BT-1.5%AlN ceramic exhibits a good piezoelectric constant of 305 pC N(-1) and an improved Vickers hardness of 5.9 GPa. The enhanced piezoelectricity originates from interactions between defect dipoles and spontaneous polarization inside the domains due to the occurrence of local symmetry, caused by the preferential distribution of the Al(3+)-N(3-) pairs vertical to the c axis. The hardening of the material is attributed to the improved density, and particle and grain boundary strengthening. Our work indicates that if a suitable doping ion pair is designed, lead-free ceramic systems prepared from ordinary raw materials by a conventional sintering method have a high probability of exhibiting good piezoelectric and mechanical properties simultaneously.


Assuntos
Compostos de Alumínio/química , Compostos de Bário/química , Cerâmica/química , Sistemas Microeletromecânicos/métodos , Titânio/química , Força Compressiva , Cristalização , Condutividade Elétrica , Campos Eletromagnéticos , Dureza , Teste de Materiais , Estresse Mecânico
17.
BMC Anesthesiol ; 14: 17, 2014 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-24612850

RESUMO

BACKGROUND: The volatile anesthetic isoflurane protects the heart from hypoxia/reperfusion (H/R) injury. However, it is still incompletely understood whether isoflurane exerts its protective role through preventing mitochondrial permeability transition pore (MPTP) opening. METHODS: Primary cultured cardiocytes were exposed to H/R in the absence or presence of isoflurane. Cell cytotoxicity and apoptosis were detected by MTT assay and TUNEL staining, respectively. MPTP function was monitored by confocal imaging after reoxygenation. ROS production and activation of caspase-3 were determined by fluorescent reader and western blot, respectively. RESULTS: As compared to the control group, H/R led to significant cell cytotoxicity and apoptosis, while application of isoflurane markedly reversed the effects. Furthermore, isoflurane significantly inhibits the formation of H/R-induced excess ROS production. Finally, isoflurane attenuated the onset of mitochondrial permeability transition pore (MPTP) occurred during hypoxia/reoxygenation, and in turn inhibited activation of caspase-3. CONCLUSIONS: These data indicate that isoflurane has a protective effect on cardiocytes exposed to H/R by reducing excess ROS production, blocking open of MPTP and further reducing apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Isoflurano/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Miócitos Cardíacos/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Apoptose/fisiologia , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Células Cultivadas , Masculino , Mitocôndrias Cardíacas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley
18.
J Control Release ; 368: 466-480, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452820

RESUMO

Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.


Assuntos
Lipossomos , Placenta , Humanos , Feminino , Gravidez , Animais , Camundongos , Lipossomos/metabolismo , Tadalafila/uso terapêutico , Tadalafila/metabolismo , Placenta/metabolismo , Placenta/patologia , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/patologia , Distribuição Tecidual , Fator de Crescimento Placentário/metabolismo , Perfusão
19.
Int J Nanomedicine ; 19: 1055-1076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322754

RESUMO

During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Colesterol/metabolismo , Carcinogênese , Transformação Celular Neoplásica , Proliferação de Células , Microambiente Tumoral
20.
Int J Nanomedicine ; 18: 3035-3046, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37312935

RESUMO

Angiogenesis is an essential mechanism for the progression of gynecological cancers. Although approved anti-angiogenic drugs have demonstrated clinical efficacy in treating gynecological cancers, the full potential of therapeutic strategies based on tumor blood vessels has not yet been realized. This review summarizes the latest angiogenesis mechanisms involved in the progression of gynecological cancers and discusses the current clinical practice of approved anti-angiogenic drugs and related clinical trials. Given the close relationship between gynecological cancers and blood vessels, we highlight more delicate strategies for regulating tumor vessels, including wise drug combinations and smart nano-delivery platforms to achieve highly efficient drug delivery and overall vessel microenvironment regulation. We also address current challenges and future opportunities in this field. We aim to generate interest in therapeutic strategies that target blood vessels as a key entry point and offer new potential and inspiration for combating gynecological cancers.


Assuntos
Inibidores da Angiogênese , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Microambiente Tumoral
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