RESUMO
Ursolic acid (UA) has shown great potential in cancer therapy but their efficacy is seriously compromised by poor water-solubility and limited cellular uptake. In this paper, cationic nanomicelles self-assembled from Pluronic F127 with the cationic polymer of C18-polyethylenimine (C18-PEI) as a functional component are fabricated as delivery vehicles of Chinese herbal medicine active components of ursolic acid (UA) for colorectal cancer treatment. The inhibition effects of this drug loaded cationic nanomicelles (named as FUP) on cell viability and cell colony formation were more significant than the free UA, due to their cationic surface which can increase UA uptake by colorectal cancer cells. Cell cycle analysis showed that this inhibition effect was mediated by a cell cycle arrest at the G1 checkpoint, and the cell death induced by these nanomicelles occurred via apoptosis, which was detected by annexin V antibody and propidium iodide staining. Further western blot analysis demonstrated the apoptosis mechanism was associated with the regulation of Fas/FasL and activation of caspase-8 and caspase-3. Therefore, our cationic nanomicelles can potentially be used to enhance the therapeutic effect of UA for colorectal cancer treatment.
RESUMO
Multifunctional nanomaterials with the magnetic resonance imaging (MRI) guided tumor photothermal ablation ability have been extensively applied in biomedical research as one of the most exciting and challenging strategies for cancer treatment. Nevertheless, most of these nanomaterials still suffer from low accumulation in tumor tissues and insufficient photothermal ablation of tumors so far. Here, we report a novel approach to overcome these limitations using a core-shell magnetite nanocluster@poly(dopamine)-PEG@ICG nanobead compositing of magnetite nanocluster core with coating of poly(dopamine), then further conjugating with polyethylene glycol (PEG) and adsorbing indocyanine green (ICG) on the surface. The adsorbed ICG in the nanobead displays a higher photostability and photothermal conversion ability than free ICG, as well as additional photothermal effect rather than magnetite nanocluster and poly(dopamine), which endow the nanobead with enhanced photothermal killing efficiency against cancer cells under near-infrared (NIR) laser irritation. Furthermore, it is proved that these nanobeads have excellent biocompatibility, T2-weighted MR imaging and magnetic field targeting ability. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced accumulation is observed at tumor site as proved by a darker T2-weighted MR image. Utilizing the magnetic targeting strategy, enhanced photothermal tumor ablation was achieved under laser irradiation in vivo, which is reflected by the degree of tumor tissue damage and tumor growth delay. Therefore, this nanobead integrates the abilities of magnetic field-targeting, MR imaging and photothermal cancer therapy, and might be a promising theranostic platform for tumor treatment.
Assuntos
Verde de Indocianina/química , Indóis/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Fototerapia/métodos , Polietilenoglicóis/química , Polímeros/química , Animais , Sobrevivência Celular/efeitos da radiação , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Terapia com Luz de Baixa Intensidade , Campos Magnéticos , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Espectroscopia de Infravermelho com Transformada de Fourier , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.
Assuntos
Hipertermia Induzida/métodos , Indóis/uso terapêutico , Nanoconjugados/administração & dosagem , Nanosferas/administração & dosagem , Fotoquimioterapia/métodos , Polímeros/uso terapêutico , Porfirinas/uso terapêutico , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Clorofilídeos , Terapia Combinada/métodos , Difusão , Células Hep G2 , Humanos , Indóis/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoconjugados/química , Nanosferas/química , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/químicaRESUMO
A novel alumina nanowire (ANW) solid-phase microextraction (SPME) fiber coating was prepared by a simple and rapid anodization-chemical etching method for ultra-selective determination of volatile esters and alcohols from complicated food samples. Preparation conditions for ANW SPME fiber coating including corrosion solution concentration and corrosion time were optimized in detail for better surface morphology and higher surface area based on scanning electron microscope (SEM). Under the optimum conditions, homogeneous alumina nanowire structure of ANW SPME fiber coating was achieved with the average thickness of 20 µm around. Compared with most of commercial SPME fiber coatings, ANW SPME fiber coatings achieved the higher extraction capacity and special selectivity for volatile esters and alcohols. Finally, an efficient gas sampling technique based on ANW SPME fiber coating as the core was established and successfully applied for the ultra-selective determination of trace volatile esters and alcohols from complicated banana and fermented glutinous rice samples coupled with gas chromatography/mass spectrometry (GC/MS) detection. It was interesting that 25 esters and 2 alcohols among 30 banana volatile organic compounds (VOCs) identified and 4 esters and 7 alcohols among 13 identified VOCs of fermented glutinous rice were selectively sampled by ANW SPME fiber coatings. Furthermore, new analytical methods for the determination of some typical volatile esters and alcohols from banana and fermented glutinous rice samples at specific storage or brewing phases were developed and validated. Good recoveries for banana and fermented glutinous rice samples were achieved in range of 108-115% with relative standard deviations (RSDs) of 2.6-6.7% and 80.0-91.8% with RSDs of 0.3-1.3% (n=3), respectively. This work proposed a novel and efficient gas sampling technique of ANW SPME which was quite suitable for ultra-selectively sampling trace volatile esters and alcohols from complicated food samples.
Assuntos
Óxido de Alumínio/química , Análise de Alimentos/instrumentação , Análise de Alimentos/métodos , Nanofios/química , Microextração em Fase Sólida/instrumentação , Compostos Orgânicos Voláteis/análise , Álcoois/análise , Álcoois/química , Álcoois/isolamento & purificação , Ésteres/análise , Ésteres/química , Ésteres/isolamento & purificação , Musa/química , Oryza/química , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificaçãoRESUMO
In the study, nanoporous array anodic alumina (NAAA) prepared by a simple, rapid and stable two-step anodic oxidization method was introduced as a novel solid-phase microextraction (SPME) fiber coating. The regular nanoporous array structure and chemical composition of NAAA SPME fiber coating was characterized and validated by scanning electron microscopy and energy dispersive spectroscopy, respectively. Compared with the commercial polydimethylsiloxane (PDMS) SPME fiber coating, NAAA SPME fiber coating achieved the higher enrichment capability (1.7-4.7 folds) for the mixed standards of volatile organic compounds (VOCs). The selectivity for volatile alcohols by NAAA SPME fiber coating demonstrated an increasing trend with the increasing polarity of alcohols caused by the gradually shortening carbon chains from 1-undecanol to 1-heptanol or the isomerization of carbon chains of some typical volatile alcohols including 2-ethyl hexanol, 1-octanol, 2-phenylethanol, 1-phenylethanol, 5-undecanol, 2-undecanol and 1-undecanol. Finally, NAAA SPME fiber coating was originally applied for the analysis of biological VOCs of Bailan flower, stinkbug and orange peel samples coupled with gas chromatography-mass spectrometry (GC-MS) detection. Thirty, twenty-seven and forty-four VOCs of Bailan flower, stinkbug and orange peel samples were sampled and identified, respectively. Moreover, the contents of trace 1-octanol and nonanal of real orange peel samples were quantified for the further method validation with satisfactory recoveries of 106.5 and 120.5%, respectively. This work proposed a sensitive, rapid, reliable and convenient analytical method for the potential study of trace and small molecular biological VOCs by the novel NAAA SPME fiber coating.
Assuntos
Óxido de Alumínio/química , Nanotecnologia/instrumentação , Microextração em Fase Sólida/métodos , Compostos Orgânicos Voláteis/análise , Eletrodos , Flores/química , Magnoliopsida/química , Porosidade , Microextração em Fase Sólida/instrumentação , Propriedades de SuperfícieRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Compound Xuanju Capsule (CXC) in the treatment of chronic prostatitis with erectile dysfunction (ED). METHODS: We obtained NIH-CPSI and IIEF-5 scores from 132 chronic prostatitis patients with ED and divided the patients into a control (n = 70) and a treatment group (n = 62), the former treated with oral levofloxacin 0.2 g bid for 4-6 weeks and oral Terazosin at 2 mg qd for 2 months, and the latter with oral CXC once 2 capsules tid for 2 months in addition to the above. RESULTS: None of the patients had serious medication-related adverse reactions. After treatment, the control group showed significantly decreased NIH-CPSI scores and slightly increased IIEF-5 scores as compared with the baseline (16.5 +/- 5.9 vs 25.1 +/- 5.5, P < 0.05 and 13.1 +/- 5.2 vs 11.3 +/- 4.5, P > 0.05), while the treatment group exhibited significant improvement in both NIH-CPSI (13.4 +/- 5.7 vs 25.5 +/- 5.3, P < 0.05) and IIEF-5 scores (17.5 +/- 6.5 vs 10.8 +/- 3.8, P < 0.05). The total effectiveness rate for ED was significantly higher in the treatment than in the control group (74.2% vs 20%, P < 0.05). CONCLUSION: Compound Xuanju Capsule can significantly alleviate both the symptoms of chronic prostatitis and ED in the treatment of chronic prostatitis patients with ED.