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1.
Nanoscale ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32195531

RESUMO

Development of multifunctional theranostics is of great significance for cancer management. Herein, we develop polyethylene glycol (PEG) modified cobalt carbide nanoparticles (Co2C-PEG NPs) as cancer photothermal theranostic agents for multimodal imaging and photothermal therapy (PTT). Co2C NPs are synthesized by a high-temperature thermal decomposition method. Afterwards, the morphology, photothermal effect, multimodal imaging capacities, biocompatibility, and PTT efficacy of Co2C-PEG NPs are carefully investigated. The as-prepared Co2C-PEG NPs exhibit high photothermal conversion efficiency (PCE, η = 35.7%) and good photostability. Through photoacoustic (PA), magnetic resonance (MR), and photothermal (PT) tri-modal imaging, in vivo pharmacokinetics and tumor temperature elevation could be monitored during the PTT process. Meanwhile, the Co2C-PEG NPs also show good PTT efficacy both in vitro and in vivo. Our findings suggest that Co2C-PEG NPs are effective for cancer photothermal theranostics.

2.
Biomaterials ; 216: 119280, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228705

RESUMO

Harsh photothermal temperatures, long-term body retention of nanoagents, elevated ROS and inflammation induction all threaten the normal tissues, thus hindering the translation of photothermal therapy (PTT) from bench to clinical practice. To resolve these problems, we have developed a disassembled theranostic nanodrug Qu-FeIIP based on the quercetin coordination. Herein, quercetin is not only the heat shock protein (Hsp 70) inhibitor but also the skeleton of Qu-FeIIP, realizing near-infrared light induced low-temperature PTT (45 °C) to ablate tumor completely without heat stress to normal tissues. Owing to the ROS scavenging ability of quercetin, Qu-FeIIP effectively reduces intracellular ROS and in vivo inflammatory factors (TNF-α, IL-6, IFN-γ) levels. Simultaneously, quercetin-Fe coordination is weakened when scavenging ROS, which triggers the Qu-FeIIP disassembling, resulting in effective clearance of nanoparticles from main organs 168 h post intravenous injection. Additionally, the photoacoustic and magnetic resonance dual-imaging capability of Qu-FeIIP offers excellent spatial resolution and imaging depth not only for precise tumor diagnosis but also for monitoring the nanodrug disassembling in vivo. Thus, Qu-FeIIP intrinsically integrates precise diagnosis, excellent low-temperature PTT efficacy, ROS elimination and anti-inflammatory action, dynamic disassembly and renal clearance ability into a single nanodrug, which is very promising for future clinical cancer treatment.

3.
J Gastrointest Surg ; 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161593

RESUMO

BACKGROUND: Obesity may impact surgical outcomes of gastrectomy. Whether visceral fat area (VFA) is a better obesity parameter than body mass index (BMI) is still controversial. The aim of this study is to compare the accuracy and effectiveness of VFA and BMI in predicting the short-term surgical outcomes of gastrectomy. METHODS: Patients who were diagnosed with gastric cancer were measured for BMI and VFA preoperatively and then divided into a VFA-H (VFA-high) group and VFA-L (VFA-low) group, at the cutoff point of 100 cm2, and a BMI-H (BMI-high) group and BMI-L (BMI-low) group, at the cutoff point of 25 kg/m2. The short-term surgical outcomes were compared between the different groups. RESULTS: In total, 276 patients were enrolled in this study; 55 (19.9%) patients were classified into the BMI-H group, and 122 (44.2%) patients were classified into the VFA-H group. There was a significant correlation between BMI and VFA (r = 0.652, p < 0.001). Compared with the VFA-L group, the VFA-H group had a higher incidence of postoperative complications (31.1% vs. 13.0%; p < 0.001), longer operation duration (270.0 (235.0-305.0) vs. 255.0 (223.8-295.0), p = 0.046), and more blood loss (100.0 (100.0-150.0) vs. 80.0 (80.0-100.0), p < 0.001), while the BMI-H group had more blood loss than the BMI-L group (100.0 (100.0-120.0) vs. 100.0(80.0-100.0), p = 0.006). Logistic regression showed that VFA was an independent risk factor for postoperative complications (odds ratio 2.813, 95% CI 1.523-5.194; p = 0.001). CONCLUSION: For gastric cancer patients, VFA is superior to BMI in accurately and effectively illuminating the impact of obesity on short-term surgical outcomes. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02800005.

4.
Angew Chem Int Ed Engl ; 58(22): 7450-7453, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-30942948

RESUMO

An enantioselective catalytic alkoxylation/oxidative rearrangement of allylic alcohols has been established by using a Brønsted acid and chiral organoiodine. The presence of 20 mol % of an (S)-proline-derived C2 -symmetric chiral iodine led to enantioenriched α-arylated ß-alkoxylated ketones in good yields and with high levels of enantioselectivity (84-94 % ee).

5.
Chemistry ; 25(28): 7012-7022, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30913329

RESUMO

The chemo-anti-inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated IrIII complexes Ir2 and Ir3 formed by conjugation of Ir1 with two antiphlogistics (aspirin and salicylic acid) have been designed. Ir2 and Ir3 exhibit higher antitumor and anti-inflammatory potencies than a mixture of Ir1 and aspirin/salicylic acid. We show that they can be hydrolyzed, accumulate in mitochondria, and induce mitochondrial dysfunction. Due to their intense long-lived phosphorescence, Ir2 and Ir3 can track mitochondrial morphological changes. Phosphorescence lifetime imaging shows that Ir2 and Ir3 can aggregate during mitochondrial dysfunction. As expected, Ir2 and Ir3 exhibit immunomodulatory properties by regulating the activity of immune factors. Both Ir2 and Ir3 can induce caspase-dependent apoptosis and caspase-independent paraptosis and inhibit several events related to metastasis. Moreover, Ir2 and Ir3 show potent tumor growth inhibition in vivo. Our study demonstrates that the combination of mitochondrial-targeting and immunomodulatory activities is feasible to develop multifunctional metal-based anticancer agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Aspirina/uso terapêutico , Complexos de Coordenação/uso terapêutico , Imunomodulação/efeitos dos fármacos , Irídio/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aspirina/química , Aspirina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Feminino , Humanos , Irídio/química , Irídio/farmacologia , Medições Luminescentes/métodos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Imagem Óptica/métodos
6.
Chem Sci ; 10(5): 1285-1293, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30809342

RESUMO

Precise quantitative measurement of viscosity at the subcellular level presents great challenges. Two-photon phosphorescence lifetime imaging microscopy (TPPLIM) can reflect micro-environmental changes of a chromophore in a quantitative manner. Phosphorescent iridium complexes are potential TPPLIM probes due to their rich photophysical properties including environment-sensitive long-lifetime emission and high two-photon absorption (TPA) properties. In this work, a series of iridium(iii) complexes containing rotatable groups are developed as mitochondria-targeting anticancer agents and quantitative viscosity probes. Among them, Ir6 ([Ir(ppy-CHO)2(dppe)]PF6; ppy-CHO: 4-(2-pyridyl)benzaldehyde; dppe: cis-1,2-bis(diphenylphosphino)ethene) shows satisfactory TPA properties and long lifetimes (up to 1 µs). The emission intensities and lifetimes of Ir6 are viscosity-dependent, which is mainly attributed to the configurational changes in the diphosphine ligand as proved by 1H NMR spectra. Ir6 displays potent cytotoxicity, and mechanism investigations show that it can accumulate in mitochondria and induce apoptotic cell death. Moreover, Ir6 can induce mitochondrial dysfunction and monitor the changes in mitochondrial viscosity simultaneously in a real-time and quantitative manner via TPPLIM. Upon Ir6 treatment, a time-dependent increase in viscosity and heterogeneity is observed along with the loss of membrane potential in mitochondria. In summary, our work shows that multifunctional phosphorescent metal complexes can induce and precisely detect microenvironmental changes simultaneously at the subcellular level using TPPLIM, which may deepen the understanding of the cell death mechanisms induced by these metallocompounds.

7.
Surg Endosc ; 33(5): 1674-1682, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30478700

RESUMO

BACKGROUND: The preoperative work-up has limitations on finding peritoneal dissemination (PD) in gastric cancer patients. Laparoscopic exploration (LE) can discover radiographically occult PD, obtain accurate stage and avert futile laparotomy. The aim of our study was to introduce "Four-Step Procedure" LE in West China Hospital and further evaluate its safety and feasibility. METHODS: We conducted a retrospective analysis on 165 patients from July 2016 to December 2017 who underwent "Four-Step Procedure" LE in gastrointestinal surgery department of West China Hospital. All the patients were diagnosed with gastric adenocarcinoma without explicit distant metastasis through Computed Tomography and/or Gastrointestinal Ultrasonography. Peritoneal lavage cytological examination (CY) was routinely performed during LE in our research. The "Four-Step" technical process of LE was introduced comprehensively. The clinicopathologic features and the presence of PD or CY at LE were analyzed, and the stratified analysis by cT and cN stages on the proportion of P1 and/or CY1 was also reported in this study. RESULTS: Total of 165 patients accepted LE in our study, among these patients: 27 (16.4%) patients with P1 and/or CY1: 19 (11.5%) patients were found PD (P1), 17 (10.3%) patients with positive cytological examination (CY1) and 9 (3.6%) patients with P1Cy1. The stratified analysis by cT stage indicated that there was no P1 and/or Cy1 in cT1-cT2 stages, 1 (2.7%) patient with P1 and 1 (2.7%) with Cy1 in cT3 stage, 18 (20.0%) patients with P1 and 16 (17.8%) with Cy1 in cT4 stage. After LE, there were 74 (44.8%) patients underwent laparoscopic assistant gastrectomy, 25 (15.2%) patients with open gastrectomy, 50 (30.3%) patients with neoadjuvant chemotherapy and 16 (9.7%) patients with palliative chemotherapy and/or conversion therapy. CONCLUSION: "Four-Step Procedure" LE is reliable and feasible for gastric cancer. From our study, LE has unique superiority on ascertaining PD and cytological examination and LE should be recommended in cT4 stage gastric cancer before resection.

8.
Nanoscale ; 10(47): 22252-22262, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30465053

RESUMO

Nano-drug delivery systems with multi-modality imaging capacities are worth pursuing because they integrate diagnostic and therapeutic functions. Herein, we report the design, synthesis and evaluation of modified iridium sulfide (IrSx) nanoparticles (NPs) for cancer therapy in vitro and in vivo. This nanosystem was prepared by modifying IrSx with polyethylene glycol (PEG) conjugated to the targeting ligand folate (FA) for multimodal imaging-guided combined chemo-photothermal therapy. Upon PEG modification, the small IrSx NPs (about 4 nm) self-assembled into much larger (about 120 nm) IrSx-PEG-FA NPs, which exhibited high photostability, ideal photothermal effect, high drug loading and pH-/photothermal-responsive drug release properties. By using the model anticancer drug camptothecin (CPT), we demonstrated that CPT@IrSx-PEG-FA can effectively target FA-receptor-positive cancer cells in vitro and show efficient tumor accumulation in vivo. The combination of CPT@IrSx-PEG-FA treatment and irradiation with an 808 nm laser resulted in complete tumor elimination. Moreover, photothermal/photoacoustic (PA)/computed tomography (CT) imaging provided an effective means to monitor the therapeutic effects. Interestingly, the nanoparticles can be cleared, resulting in low systematic toxicity of CPT@IrSx-PEG-FA. Our work demonstrates that the as-prepared IrSx-PEG-FA NPs present a promising platform for the construction of multifunctional theranostic agents for cancer therapy.


Assuntos
Camptotecina/administração & dosagem , Receptor 1 de Folato/química , Nanopartículas/química , Fototerapia , Polietilenoglicóis/química , Animais , Antineoplásicos/administração & dosagem , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ácido Fólico , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida , Irídio , Células MCF-7 , Camundongos , Imagem Multimodal , Nanopartículas/uso terapêutico , Técnicas Fotoacústicas , Sulfetos , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X
9.
Adv Sci (Weinh) ; 5(10): 1800581, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30356964

RESUMO

Recently, phosphorescent iridium complexes have demonstrated great potential as anticancer and imaging agents. Dopamine is a melanin-like mimic of mussel adhesive protein that can self-polymerize to form polydopamine (PDA) nanoparticles that demonstrate favorable biocompatibility, near-infrared absorption, and photothermal effects. Herein, PDA nanoparticles are functionalized with ß-cyclodextrin (CD) substitutions, which are further assembled with adamantane-modified arginine-glycine-aspartic acid (Ad-RGD) tripeptides to target integrin-rich tumor cells. The thus formed PDA-CD-RGD nanoparticles can deliver a phosphorescent iridium(III) complexes LysoIr ([Ir(ppy)2(l)]PF6, ppy = 2-phenylpyridine, L = (1-(2-quinolinyl)-ß-carboline) to form a theranostic platform LysoIr@PDA-CD-RGD. It is demonstrated that LysoIr@PDA-CD-RGD can be applied for targeted combined cancer photothermal-chemotherapy and thermal/photoacoustic/two-photon phosphorescence lifetime imaging under both in vitro and in vivo conditions. This work provides a useful strategy to construct multifunctional nanocomposites for the optimization of metal-based anticancer agents for further biomedical applications.

10.
Chemistry ; 24(71): 18971-18980, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30264929

RESUMO

Emerging studies have shown that mitochondrial DNA (mtDNA) is an attractive target for anticancer therapeutics. Herein, a heterobimetallic complex [Ru(dip)2 (µ-bpm)PtCl2 ]Cl2 (RuPt; dip=4,7-diphenyl-1,10-phenanthroline; bpm=2,2'-bipyrimidine) and the corresponding mononuclear complex [Ru(dip)2 (bpm)]Cl2 (Ru) have been designed and synthesized. RuPt can bind to mtDNA and damage it both in the dark and upon visible light irradiation. By using a variety of methods, it was demonstrated that RuPt can interfere with the function of mtDNA by decreasing the amplification and copy number of mtDNA, and affecting the transcriptional level of mitochondria-encoded genes. Furthermore, RuPt can disturb the physiological processes of mitochondria and induce caspase-dependent apoptosis in the presence of light. In addition, RuPt shows low systemic toxicity and potent in vivo anticancer potency upon light irradiation. This study provides strong evidence that mtDNA is an important molecular target of RuPt, and photodamaging mtDNA is an effective strategy to overcome cisplatin resistance.


Assuntos
Dano ao DNA/efeitos dos fármacos , DNA Mitocondrial/genética , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/farmacologia , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Cisplatino/química , Cisplatino/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Células HeLa , Humanos , Neoplasias/genética , Compostos Organoplatínicos/química , Fenantrolinas/química , Fenantrolinas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Pirimidinas/química , Pirimidinas/farmacologia , Rutênio/química
11.
Biomaterials ; 185: 73-85, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30227273

RESUMO

A promising theranostic nanosystem VK3-CPT@Ru-CD is designed and fabricated by the host-guest driven self-assembly between the fluorescent adamantine-functionalized Ru(II) complexes and the ROS-labile-cyclodextrin modified thioketal linkers, in which anticancer drug camptothecin (CPT) and vitamin K3 (VK3) are effectively co-encapsulated. On account of the generative feedback between the intracellular redox cycling of VK3 and the high degree of ROS-triggered collapse of nanoparticles, VK3-CPT@Ru-CD can facilitate cancer-specific ROS amplification and drug release selectively in cancer cells, thus realizing the selective killing of tumor with minimal side-effects both in vitro and in vivo, the therapeutic effect of which is more prominent than the free anti-cancer drugs. More interestingly, the menadione structure of encapsulated VK3 can effectively quench the inherent fluorescence of Ru-CD, and a fluorescence lightening up phenomenon is observed accompanied with the ROS-triggered drug release, which can be utilized for real-time tracking of drug release in vitro and in vivo.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Camptotecina/administração & dosagem , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Vitamina K 3/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Complexos de Coordenação/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanomedicina Teranóstica/métodos , Vitamina K 3/farmacocinética , Vitamina K 3/uso terapêutico
12.
J Cell Mol Med ; 22(11): 5504-5517, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30091830

RESUMO

Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT3 overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.


Assuntos
Envelhecimento/genética , Infarto do Miocárdio/genética , Isquemia Miocárdica/genética , Sirtuína 3/genética , Envelhecimento/patologia , Animais , Antioxidantes , Medula Óssea/metabolismo , Catalase/genética , Terapia Baseada em Transplante de Células e Tecidos/métodos , Proteína Forkhead Box O3/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/terapia , Estresse Oxidativo/genética , Plasmídeos/genética , Substâncias Protetoras , Ratos , Espécies Reativas de Oxigênio , Sirtuína 3/administração & dosagem , Superóxido Dismutase/genética , Transfecção
13.
Anal Chem ; 90(14): 8304-8308, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-29963850

RESUMO

Miniaturized sample pretreatment platforms have simplified analytical tasks in diverse disciplines. Herein, a novel pipet microextraction (PME) device is reported by making use of the photothermal property of a light-heatable sorbent (LHS) for the first time. Efficient and staining-free heating treatment of small volumes of liquids confined in the PME device is now enabled through light illumination. The light-induced heating treatment is capable of dramatically accelerating solvent elution rates, effectively unlocking bound toxin from its antibody, and rapidly quenching enzymatic activities, thus, provides PME with higher efficiencies and enables its new applications in antibody-intermediated sampling of targeted toxin from stained food surfaces and powders, as well as in accurate revelation of enzymatic reaction kinetics. This study offers a new perspective of designing efficient and versatile microextraction platforms and demonstrates their potential applications in different fields including public security, new drug development, and environmental protection.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29885513

RESUMO

Flos Lonicerae was an important Chinese medicine. In this research, a microwave assisted extraction method was applied for the extraction of chlorogenic acid from Flos Lonicerae. The operating conditions were optimized using a Box-Behnken design test. Under the optimal conditions, the extraction yield of chlorogenic acid reached 32.52 ±â€¯1.31 mg/g. Next, a direct analysis in real time mass spectrometry (DART-MS) method was utilized to quantify of chlorogenic acid in Flos Lonicerae extracts. The primary parameters were optimized to obtain maximum signal intensity. In the detection process of the actual samples, the results obtained by DART-MS are consistent with those obtained by HPLC method with short detection time and acceptable repeatability and precision (<15%). In addition, the DART-MS/MS method has several advantages, such as speed, low cost and simplicity. Therefore, the DART-MS method is an efficient method that can be applied in the quantification of chlorogenic acid in Flos Lonicerae.


Assuntos
Ácido Clorogênico/análise , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Caprifoliaceae/química , Ácido Clorogênico/química , Ácido Clorogênico/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Modelos Lineares , Micro-Ondas , Reprodutibilidade dos Testes
15.
PLoS One ; 13(6): e0198072, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29944667

RESUMO

Guangdong, Guangxi and Chongqing are emerging sericulture areas in China where the production of mulberry leaves is huge. In order to identity high quality mulberry leaves that are suitable for healthy products to expand planting, 24 samples from three regions (Guangdong, Guangxi, Chongqing) in the south of China were quantified for two alkaloids (1-deoxynojirimycin and fagomine) and five phenols (chlorogenic acid, rutin, isoquercitrin, etc.) using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Additionally, the total phenolic and total flavonoid contents, antioxidant and glycosidase inhibitory activities (hypoglycemic activity) were tested using different assays (DPPH, ABTS, FRAP) to comprehensively evaluate the quality of the mulberry leaves. The contents of DNJ and fagomine ranged from 0.401±0.003 to 5.309±0.036 mg/g and from 0.279±0.031 to 2.300±0.060 mg/g, respectively. The main phenolic constituents were chlorogenic acid, rutin and isoquercitrin, with chlorogenic acid present in the highest concentrations, ranging from 3.104±0.191 to 10.050±0.143 mg/g. The antioxidant activity exhibited a tendency as follows: Guangxi > Guangdong > Chongqing, except for two samples from Chongqing, which showed the highest antioxidant activity. Based on our study, mulberry leaves from Guangdong and Guangxi could be future sources of natural hypoglycemic and antioxidant products.


Assuntos
Antioxidantes/química , Hipoglicemiantes/química , Morus/química , Morus/crescimento & desenvolvimento , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Alcaloides/análise , Antioxidantes/farmacologia , China , Indústria Alimentícia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Fenóis/análise
16.
J Biomater Appl ; 32(9): 1253-1264, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29448866

RESUMO

A multimodal nanocarrier based on mesoporous silica nanoparticles (MSNs) is developed to co-delivery photosensitizer chlorin e6 (Ce6) and chemotherapeutic agent doxorubicin (Dox) for cancer combination therapy. Ce6 was covalently conjugated with mesoporous silica nanoparticles, which could increase the loading efficiency, and allowed for photodynamic therapy. Doxorubicin was loaded into the pores of mesoporous silica nanoparticles to afford the dual drug delivery system Dox@MSNs-Ce6. These hybrid nanoparticles have an average diameter of about 100 nm and slightly negative charge of about -17 mV. The Dox@MSNs-Ce6 nanoparticles could efficiently enter into cancer cells. The cellular reactive oxygen species level in treated cells increased about 17 times, upon 660 nm light irradiation (10 mW/cm2, 2 min). More importantly, Dox@MSNs-Ce6 exhibited excellent synergistic effect through combining chemotherapy and photodynamic therapy against A549 lung cancer cells. Our work provides an effective strategy for anticancer drug delivery and combination therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Dióxido de Silício/química , Células A549 , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Nanoconjugados/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia , Porosidade , Porfirinas/farmacocinética , Porfirinas/farmacologia
17.
Carbohydr Polym ; 181: 560-569, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29254008

RESUMO

In the present study, porous magnetic cellulose beads (CBs) were prepared and further modified using amines. The CBs appeared to have good spherical shape and three-dimensional (3D) porous structure. In the adsorption tests, the modified cellulose beads (MCBs) showed better adsorption capacities and shorter adsorption times on hyperin and 2'-O-galloylhyperin than the commercial resins. The adsorption may be due to the hydrogen bonding between the target compounds and the amine groups of MCBs. After adsorption and desorption, the contents of hyperin and 2'-O-galloylhyperin reached 1.32% and 3.92%, which were 4.08 and 4.23 times higher than those in the Pyrola extracts. Therefore, the prepared MCBs in this study make an excellent adsorbing material of hyperin and 2'-O-galloylhyperin, and it may have potential for the separation of other natural compounds.

18.
Nanoscale ; 9(47): 18966-18976, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29181479

RESUMO

Nanohybrids can in most cases kill cancer cells more efficiently as compared with free photosensitizers. In this work, we constructed nanohybrid Ru1@CDs composed of carbon nanodots (CDs) and a phosphorescent Ru(ii) complex (Ru1) for one- and two-photon photodynamic therapy of cancer. The photosensitizer and imaging agent Ru1 is decorated onto the nanocarrier CDs covalently. Ru1 and Ru1@CDs can penetrate into cancer cells through an energy-dependent mechanism and endocytosis, respectively. Both Ru1 and Ru1@CDs are capable of lysosome-targeted phosphorescence imaging and photodamage under either 450 nm (one-photon) or 810 nm (two-photon) excitation. Conjugation with CDs can increase the cellular uptake efficacy of Ru1. Mechanism investigations show that both Ru1 and Ru1@CDs can induce apoptosis through generation of reactive oxygen species and cathepsin-initiated apoptotic signaling pathways. Upon two-photon excitation, Ru1@CDs show better penetrability, as well as higher inhibitory effects on cancer cell growth in both 2D cell and 3D multicellular tumor spheroid models. Our work provides an effective strategy for the construction of multifunctional imaging and phototherapeutic nanohybrids for the treatment of cancer.


Assuntos
Carbono , Lisossomos , Nanoestruturas , Fotoquimioterapia , Rutênio/química , Células A549 , Animais , Apoptose , Complexos de Coordenação , Embrião não Mamífero , Endocitose , Humanos , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares , Peixe-Zebra
19.
Dis Markers ; 2017: 8241953, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28947845

RESUMO

OBJECTIVE: To examine the relationship between the Sirtuin-3 (SIRT3) expression and the clinical indicators/prognosis of patients with non-small-cell lung cancer (NSCLC). METHODS: The mRNA level of SIRT3 was detected by real-time PCR, while the protein level was detected by Western blot and immunohistochemical staining. SPSS 16.0 software was used for statistical analysis. RESULTS: The expression of SIRT3 was significantly higher in NSCLC tissue than in adjacent tissue. The SIRT3 level was correlated significantly with lymph node metastasis and clinical stage of NSCLC patients. Moreover, univariate analysis showed that the expression of SIRT3, tumor size, lymph node metastasis, degree of differentiation, and clinical stage were correlated with the prognosis of NSCLC patients. Multivariate analysis demonstrated that lymph node metastasis, the tumor size, and SIRT3 expression were independent prognostic factors for NSCLC patients. CONCLUSIONS: SIRT3 is associated with the development and progression of NSCLC. The SIRT3 expression can be used as an independent prognostic factor for NSCLC patients and help identify prognosis of NSCLC. Therefore, SIRT3 has the potential to become a new factor for prognosis prediction and personalized treatment of NSCLC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Sirtuína 3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sirtuína 3/genética
20.
Dalton Trans ; 46(34): 11395-11407, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28813052

RESUMO

Many phosphorescent iridium complexes are potent candidates as photodynamic therapeutic agents. In this work, a series of mixed-ligand phosphorescent iridium complexes (Ir1: [Ir(L1)(bpy)Cl](PF6)2; Ir2: [Ir(L1)(ppy)Cl](PF6); Ir3: [Ir(L2)(bpy)Cl](PF6)2; Ir4: [Ir(L2)(ppy)Cl](PF6). L1 = 2,6-bis(2-benzimidazolyl)pyridine; bpy = 2,2'-bipyridine; L2 = 2,6-bis(1-methyl-benzimidazol-2-yl)pyridine; ppy = 2-phenylpyridine) have been synthesized and characterized. These complexes display high luminescence quantum yields and long phosphorescence lifetimes. All the complexes are resistant to hydrolysis in aqueous solutions, and can produce singlet oxygen (1O2) effectively upon irradiation. Ir1 and Ir2 show pH-sensitive emission properties. Interestingly, higher cellular uptake efficiency is observed for Ir2 and Ir4 with the cyclometalated ppy ligand in human lung adenocarcinoma A549 cells. Ir2 with pH-sensitive emission properties can selectively image lysosomes, and Ir4 can specifically target mitochondria. Both Ir2 and Ir4 exhibit potent photodynamic therapy (PDT) effects, with Ir2 displaying a higher phototoxicity index (PI) especially in A549 cells (PI > 54). Mechanism studies indicate that Ir2 and Ir4 can induce apoptosis through reactive oxygen species (ROS) generation and caspase activation upon visible light (425 nm) irradiation. As expected, Ir2 can damage lysosomes more effectively with a pH-sensitive singlet oxygen (1O2) yield, while Ir4 tends to impair mitochondrial function. Nevertheless, the practical application of Ir2 and Ir4 for PDT may be limited to superficial tumors due to the short excitation wavelength (425 nm). Our study gives insights into the design and anticancer mechanisms of new metal-based PDT anticancer agents.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Irídio/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Transporte Biológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação , Ligantes , Lisossomos/efeitos dos fármacos , Lisossomos/efeitos da radiação , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Compostos Organometálicos/síntese química , Compostos Organometálicos/metabolismo , Oxigênio Singlete/metabolismo , Água/química
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