RESUMO
Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.
Assuntos
Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio , Antracenos , Linhagem Celular TumoralRESUMO
The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.
Assuntos
Neoplasias da Mama , Carnosina , Humanos , Feminino , Carnosina/metabolismo , Carnosina/farmacologia , Cobre/farmacologia , Glicólise , ZincoRESUMO
Chemotherapeutic resistance poses a significant challenge in cancer treatment, resulting in the reduced efficacy of standard chemotherapeutic agents. Abnormal metabolism, particularly increased anaerobic glycolysis, has been identified as a major contributing factor to chemotherapeutic resistance. To address this issue, noninvasive imaging techniques capable of visualizing tumor glycolysis are crucial. However, the currently available methods (such as PET, MRI, and fluorescence) possess limitations in terms of sensitivity, safety, dynamic imaging capability, and autofluorescence. Here, we present the de novo design of a unique afterglow molecular scaffold based on hemicyanine and rhodamine dyes, which holds promise for low-background optical imaging. In contrast to previous designs, this scaffold exhibits responsive "OFF-ON" afterglow signals through spirocyclization, thus enabling simultaneous control of photodynamic effects and luminescence efficacy. This leads to a larger dynamic range, broader detection range, higher signal enhancement ratio, and higher sensitivity. Furthermore, the integration of multiple functionalities simplifies probe design, eliminates the need for spectral overlap, and enhances reliability. Moreover, we have expanded the applications of this afterglow molecular scaffold by developing various probes for different molecular targets. Notably, we developed a water-soluble pH-responsive afterglow nanoprobe for visualizing glycolysis in living mice. This nanoprobe monitors the effects of glycolytic inhibitors or oxidative phosphorylation inhibitors on tumor glycolysis, providing a valuable tool for evaluating the tumor cell sensitivity to these inhibitors. Therefore, the new afterglow molecular scaffold presents a promising approach for understanding tumor metabolism, monitoring chemotherapeutic resistance, and guiding precision medicine in the future.
Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Animais , Camundongos , Reprodutibilidade dos Testes , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , GlicóliseRESUMO
The total antioxidant capacity (TAC) is a key indicator of the body's resistance to oxidative stress injury in diabetic patients. The measurement of TAC is important for effectively evaluating the redox state to prevent and control the occurrence of diabetes complications. However, there is a lack of a simple, convenient, and reliable method to detect the total antioxidant capacity in diabetes. Herein, we design a novel chemiluminescent platform based on semiconducting polymer nanoparticles-manganese (SPNs-MnVII) to detect the total antioxidant capacity of urine in diabetic mice. We synthesize semiconducting polymer nanoparticles with four different structures and discover the ability of MnVII to produce singlet oxygen (1O2) that is employed to excite thiophene-based SPNs (PFODBT) to emit near-infrared chemiluminescence. Notably, the chemiluminescent intensity has a good linear relationship with the concentration of MnVII (detection limit: 2.8 µM). Because antioxidants (e.g., glutathione or ascorbic acid) can react with MnVII, such a chemiluminescent tool of SPNs (PFODBT)-MnVII can detect the glutathione or ascorbic acid with a larger responsive range. Furthermore, the total antioxidant capacity of urine from mice is evaluated via SPNs (PFODBT)-MnVII, and there are statistically significant differences between diabetic and healthy mice. Thus, this new chemiluminescent platform of SPNs (PFODBT)-MnVII is convenient, efficient, and sensitive, which is promising for monitoring antioxidant therapy of diabetes.
Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Animais , Camundongos , Antioxidantes , Ácido Ascórbico , Glutationa , Manganês/química , Nanopartículas/química , Polímeros/química , Medições LuminescentesRESUMO
Organic afterglow nanoparticles are unique optical materials that emit light long after cessation of excitation. Due to their advantages of no need for real-time light excitation, avoiding autofluorescence, low imaging background, high signal-to-background ratio, deep tissue penetration, and high sensitivity, afterglow imaging technology has been widely used in cell tracking, biosensing, cancer diagnosis, and cancer therapy, which provides an effective technical method for the acquisition of molecular information with high sensitivity, specificity and real-time at the cellular and living level. In this review, we summarize and illustrate the recent progress of organic afterglow imaging, focusing on the mechanism of organic afterglow materials and their biological application. Furthermore, we also discuss the potential challenges and the further directions of this field.
Assuntos
Nanopartículas , Neoplasias , Humanos , Diagnóstico por Imagem , Neoplasias/diagnóstico por imagem , LuminescênciaRESUMO
BACKGROUND: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.
Assuntos
Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Hepatite B , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Hepatite B/complicações , Hepatite B/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Fígado Gorduroso/complicações , Alanina Transaminase , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
BACKGROUND: COVID-19 has been reported to affect the sleep quality of Chinese residents; however, the epidemic's effects on the sleep quality of college students during closed-loop management remain unclear, and a screening tool is lacking. OBJECTIVE: This study aimed to understand the sleep quality of college students in Fujian Province during the epidemic and determine sensitive variables, in order to develop an efficient prediction model for the early screening of sleep problems in college students. METHODS: From April 5 to 16, 2022, a cross-sectional internet-based survey was conducted. The Pittsburgh Sleep Quality Index (PSQI) scale, a self-designed general data questionnaire, and the sleep quality influencing factor questionnaire were used to understand the sleep quality of respondents in the previous month. A chi-square test and a multivariate unconditioned logistic regression analysis were performed, and influencing factors obtained were applied to develop prediction models. The data were divided into a training-testing set (n=14,451, 70%) and an independent validation set (n=6194, 30%) by stratified sampling. Four models using logistic regression, an artificial neural network, random forest, and naïve Bayes were developed and validated. RESULTS: In total, 20,645 subjects were included in this survey, with a mean global PSQI score of 6.02 (SD 3.112). The sleep disturbance rate was 28.9% (n=5972, defined as a global PSQI score >7 points). A total of 11 variables related to sleep quality were taken as parameters of the prediction models, including age, gender, residence, specialty, respiratory history, coffee consumption, stay up, long hours on the internet, sudden changes, fears of infection, and impatient closed-loop management. Among the generated models, the artificial neural network model proved to be the best, with an area under curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 0.713, 73.52%, 25.51%, 92.58%, 57.71%, and 75.79%, respectively. It is noteworthy that the logistic regression, random forest, and naive Bayes models achieved high specificities of 94.41%, 94.77%, and 86.40%, respectively. CONCLUSIONS: The COVID-19 containment measures affected the sleep quality of college students on multiple levels, indicating that it is desiderate to provide targeted university management and social support. The artificial neural network model has presented excellent predictive efficiency and is favorable for implementing measures earlier in order to improve present conditions.
Assuntos
COVID-19 , Qualidade do Sono , Humanos , Estudos Transversais , COVID-19/epidemiologia , Teorema de Bayes , Estudantes , Surtos de Doenças , InternetRESUMO
Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.
Assuntos
Ferroptose , Nanoestruturas , Humanos , Linhagem Celular Tumoral , Imageamento por Ressonância Magnética , HipóxiaRESUMO
Ferroptosis exhibits potential to damage drug-resistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1 -/T2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.
Assuntos
Ferroptose , Nanopartículas , Neoplasias , Ligas , Linhagem Celular Tumoral , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias/patologia , Microambiente TumoralRESUMO
The high proliferation efficiency, redox imbalance, and elevated nucleic acid repair capabilities of tumor cells severely restrict the theranostic efficacy. Selectively interference chaotic tumors with devastating nucleic acid damages (NUDs) properties are expected to overcome theranostic barriers. Here, an exquisite catalytic-based strategy with comprehensive NUDs mechanisms is demonstrated. In this regard, enzyme (glucose oxidase, GOD) symbioses nanozyme Cu3+x (PO4 )2 through biomineralization (abbreviated as Cu@GOD), GOD can disorder the metabolism by consuming glucose, thereby inhibiting the nutrition supply for nucleic acid repair. GOD-catalyzed H2 O2 guarantees the self-cyclic glutathione depletion and reactive oxygen species generation caused by Cu3+x (PO4 )2 , resulted the reduced antioxidation defense and enhanced oxidation assault, ensures an indiscriminate NUDs ability. Moreover, the high photothermal effect of Cu3+x (PO4 )2 induces effective tumor inhibition. Consequently, this substantial multipath NUDs strategy, with potentials of suppressing the cytoprotective mechanisms, amplifying the cellular oxidative stress, and disrupting the redox balance to ensure substantial irreversible NUDs, completely breaks the obstacle of chaotic tumors, providing new conceptual thinking for tumor proliferation inhibition.
Assuntos
Neoplasias , Ácidos Nucleicos , Catálise , Glucose Oxidase , Humanos , Microambiente TumoralRESUMO
In chemodynamic therapy (CDT), real-time monitoring of reactive oxygen species (ROS) production is critical to reducing the nonspecific damage during CDT and feasibly evaluating the therapeutic response. However, CDT agents that can emit ROS-related signals are rare. Herein, we synthesize a semiconducting polymer nanoplatform (SPN) that can not only produce highly toxic ROS to kill cancer cells but also emit ROS-correlated chemiluminescent signals. Notably, the efficacy of both chemiluminescence and CDT can be significantly enhanced by hemin doping (â¼10-fold enhancement for luminescent intensity). Such ROS-dependent chemiluminescence of SPN allows ROS generation within a tumor to be optically monitored during the CDT process. Importantly, SPN establishes an excellent correlation of chemiluminescence intensities with cancer inhibition rates in vitro and in vivo. Thus, our nanoplatform represents the first intelligent strategy that enables chemiluminescence-imaging-monitored CDT, which holds potential in assessing therapeutic responsivity and predicting treatment outcomes in early stages.
Assuntos
Medições Luminescentes , Neoplasias Experimentais , Fotoquimioterapia , Polímeros/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismoRESUMO
We developed a cyclic amplification method for an organic afterglow nanoreporter for the real-time visualization of self-generated reactive oxygen species (ROS). We promoted semiconducting polymer nanoparticles (PFODBT) as a candidate for emitting near-infrared afterglow luminescence. Introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen (1 O2 ). 1 O2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage-related molecular patterns, thereby evoking immunogenic cell death (ICD)-associated immune responses through ROS-based oxidative stress. The afterglow luminescent signals of the nanoreporter were well correlated with light-driven 1 O2 generation and anti-cancer efficiency. This imaging strategy provides a non-invasive tool for predicting the therapeutic outcome that occurs during ROS-mediated cancer therapy.
Assuntos
Luminescência , Nanopartículas/metabolismo , Neoplasias/metabolismo , Polímeros/metabolismo , Humanos , Nanopartículas/química , Neoplasias/patologia , Polímeros/química , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete/química , Oxigênio Singlete/metabolismoRESUMO
Chemodynamic therapy is an emerging tumor therapeutic strategy. However, the anticancer effects are greatly limited by the strong acidity requirements for effective Fenton-like reaction, and the inevitably "off-target" toxicity. Herein, we develop an acidity-unlocked nanoplatform (FePt@FeOx @TAM-PEG) that can accurately perform the high-efficient and tumor-specific catalysis for anticancer treatment, through dual pathway of cyclic amplification strategy. Notably, the pH-responsive peculiarity of tamoxifen (TAM) drug allows for the catalytic activity of FePt@FeOx to be "turn-on" in acidic tumor microenvironments, while keeping silence in neutral condition. Importantly, the released TAM within cancer cells is able to inhibit mitochondrial complex I, leading to the upregulated lactate content and thereby the accumulated intracellular H+ , which can overcome the intrinsically insufficient acidity of tumor. Through the positive feedback loop, large amount of active FePt@FeOx nanocatalyzers are released and able to access to the endogenous H2 O2 , exerting the improved Fenton-like reaction within the more acidic condition. Finally, such smart nanoplatform enables self-boosting generation of reactive oxygen species (ROS) and induces strong intracellular oxidative stress, leading to the substantial anticancer outcomes in vivo, which may provide a new insight for tumor-specific cascade catalytic therapy and reducing the "off-target" toxicity to surrounding normal tissues.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Nanopartículas de Magnetita/química , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima , Animais , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Camundongos , Estrutura Molecular , Estresse Oxidativo , Tamanho da Partícula , Espécies Reativas de Oxigênio/químicaRESUMO
Drug-induced hepatic damage has drawn great attention on public health problems. Drugs are biotransformed in the liver by enzymatic processes, accompanied by the production of reactive free radicals, which is the main cause of drug-induced hepatotoxicity. However, the limited penetration of optics makes the use of current luminescence imaging more difficult for acquiring free radicals mapping for lesion location, when applied to whole-body imaging in vivo. In this work, we develop an activatable nanoprobe based on Prussian blue (PB) that can combine magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for deep-tissue ONOO- imaging. We discover that ONOO- can oxidize FeII within PB into FeIII and meanwhile destroy the crystal structure of PB so that the strong absorption of PB at 710 nm that originated from the electron transferring between FeII and FeIII is greatly diminished. As a result, the reduced photoacoustic imaging (PA) signal of PB is able to function as an indicator for sensing ONOO-. Importantly, after reaction with ONOO-, the reduced size of PB results in the decrease of rotational correlation time (τR), leading to the activatable MRI signal for sensing ONOO-. Finally, we demonstrate that the PB nanoprobe is successfully able to image the variation of ONOO- in drug-induced hepatotoxicity in vivo by PAI and MRI bimodal imaging. Notably, the complementarity of such dual-modality imaging could not only endow our probes with better accuracy and higher penetration depth for visualizing of ONOO- in drug-induced liver injury but also provide anatomical structure to identify the injury area of livers.
Assuntos
Ferrocianetos/química , Corantes Fluorescentes/química , Imagem Molecular , Ácido Peroxinitroso/análise , Técnicas Fotoacústicas , Fenômenos Magnéticos , OxirreduçãoRESUMO
Peroxynitrite (ONOO-) is involved in neurodegenerative, inflammatory, cardiovascular disorders, cancers, and other pathological progress. However, current imaging methods for sensing ONOO- usually suffer from high background/autofluorescence for fluorescent probes and poor selectivity/short emission wavelength for chemiluminescent probes. Herein, we present a novel chemiluminescent molecule (oxygen-embedded quinoidal pentacene) responsive to ONOO- for the first time, on the basis of which we rationally construct a near-infrared nanoprobe for detecting ONOO- via chemiluminescence resonance energy transfer (CRET) mechanism. Notably, our nanoprobe exhibits good selectivity, ultrahigh sensitivity (nanomole level), low background noise, fast response, and high water solubility. Moreover, the near-infrared emission from CRET offers higher tissue penetration of the chemiluminescent signal. Finally, our nanoprobe is further successfully applied to detecting endogenous ONOO- in mice with abdominal inflammation, drug-induced hepatotoxicity, or tumor models in vivo. In summary, the self-luminescing nanoprobes can act as an alternative visualizable tool for illuminating the mechanism of ONOO- involved in the specific pathological process.
Assuntos
Corantes Fluorescentes/química , Medições Luminescentes/métodos , Naftacenos/química , Oxigênio/química , Ácido Peroxinitroso/análise , Animais , Linhagem Celular Tumoral , Feminino , Transferência Ressonante de Energia de Fluorescência , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Imagem Óptica/métodos , Ácido Peroxinitroso/metabolismo , Transplante HomólogoRESUMO
Cancer treatments are confounded by severe toxic effects toward patients. To address these issues, activatable nanoprobes have been designed for specific imaging and destruction of cancer cells under the stimulation of specific cancer-associated biomarkers. Most activatable nanoprobes were usually activated by some single-factor stimulation, but this restricts therapeutic specificity between diseased and normal tissue; therefore, multifactor activation is highly desired. To this end, we herein develop a novel dual-stimuli responsive theranostic nanoprobe for simultaneously activatable cancer imaging and photothermal therapy under the coactivation of "dual-key" stimulation of "nitric oxide (NO)/acidity", so as to further improve the therapeutic specificity. Specifically, we have integrated a weak electron acceptor (benzo[c][1,2,5]thiadiazole-5,6-diamine) into a donor-π-acceptor-π-donor type chromophore. When the weak acceptor was oxidized by NO in acidic conditions to form a stronger acceptor (5H-[1,2,3]triazolo[4,5-f]-2,1,3-benzothiadiazole), the molecule absorption was significantly increased in the near-infrared region, based on the intramolecular charge transfer (ICT) mechanism. Under the dual-key stimulation of NO/acidity within the tumor associated with inflammation, the nanoprobe can correspondingly output dual signals for ratiometric photoacoustic and photothermal imaging of cancer in vivo and do so with enhanced accuracy and specificity. Our novel nanoprobe exhibited higher photoacoustic signal enhancement under dual-factor activation at 9.8 times that of NO and 132 times that of acidity alone, respectively. Moreover, through such dual activation of NO/acidity, the nanoprobe produces more differentiation of hyperthermia between tumor and normal tissues, to afford satisfactory photothermal therapy with minimal toxic side effects. Thus, our work presents a promising strategy for significantly improving the precision and specificity of cancer imaging and therapy.
Assuntos
Nanopartículas/uso terapêutico , Neoplasias/terapia , Óxido Nítrico/metabolismo , Tiadiazóis/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Hipertermia Induzida , Camundongos , Imagem Molecular , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patologia , Imagem Óptica , Técnicas Fotoacústicas , Fototerapia , Nanomedicina Teranóstica , Tiadiazóis/químicaRESUMO
Photoacoustic (PA) imaging as a noninvasive biomedical imaging technology exhibits high spatial resolution and deep tissue penetration for in vivo imaging. In order to fully explore the potential of PA imaging in biomedical applications, new contrast agents with improved PA stability and efficiency are in high demand. Herein, we present a new PA agent based on an oxygen-embedded quinoidal nonacene chromophore that is self-assembled into nanoparticles (Nano(O-Nonacene)-PEG), assisted by polyethylene glycol (PEG). Notably, the photothermal conversion efficiency of Nano(O-Nonacene)-PEG is 1.5 fold that of semiconducting polymer nanoparticles (Nano(PCPDTBT)-PEG) and 2.8 fold that of Au nanorods, owing to the low quantum yield of Nano(O-Nonacene)-PEG. Thereby, Nano(O-Nonacene)-PEG possess a greatly elevated PA signal intensity, compared to Nano(PCPDTBT)-PEG and Au nanorods, which have been widely explored for PA imaging. Due to the high resistance to photo bleaching, Nano(O-Nonacene)-PEG exhibits higher PA signal stability, which may be employed for long-term PA imaging. Moreover, when magnetic Zn0.4Fe2.6O4 nanoparticles are incorporated into Nano(O-Nonacene)-PEG, not only are magnetic resonance signals generated but also the photoacoustic efficacy is greatly enhanced. Therefore, Nano(O-Nonacene)-PEG offers distinct properties: (i) the elevated photoacoustic effect allows for high-resolution photoacoustic imaging, (ii) small size (10 nm in diameter) results in efficient tumor-targeting, and (iii) the facile application of efficient photothermal therapy in vivo. The current work offers the possibility of oxygen-embedded quinoidal acene as a promising PA probe for precision phototheranostics.
Assuntos
Imagem Molecular , Sondas Moleculares/química , Nanopartículas/química , Oxigênio/química , Técnicas Fotoacústicas , Fototerapia , Quinonas/química , Estrutura Molecular , Tamanho da Partícula , Polietilenoglicóis/química , Semicondutores , Propriedades de SuperfícieRESUMO
OBJECTIVE: To determine component changes of metabolic syndrome in pre-elderly people with healthy obese phenotype. METHODS: A total of 1 686 adults aged between 45-59 yr. who underwent health examinations from 2010 to 2016 in West China Hospital of Sichuan University participated in this study. The participants had healthy obese phenotype at the baseline but no history of diabetes,high blood pressure,high cholesterol and cardiovascular disease. Component changes of metabolic syndrome (MS) and associated factors over the seven-year period were analysed using logistic regression modeling. RESULTS: The number of MS components increased over the years in centrally obese individuals,and 11.0% developed MS,including 118 men [(53.29±4.00) years old,66.95% current smokers,5.93% past smokers,24.58% alcohol drinkers] and 67 women [(52.01±4.06) years old,26.87% current smokers,1.49% past smokers,11.94% alcohol drinkers]. The most frequently presented MS components included higher fasting glucose,higher blood pressure and higher triglyceride. Healthy status (0 MS component) resumed in 44 participants who had abdominal obesity (1 MS component) at the baseline: 27 women and 17 men. Age (OR=1.732, 95%CIï¼1.594-1.882, P<0.000 1),smoking (OR=7.188, 95%CIï¼4.311-11.986, P<0.000 1) and drinking (OR=3.986, 95%CIï¼2.283-6.959, P<0.000 1) were identified as risk factors of MS. CONCLUSION: MS components increase over years in both men and women. Smoking and drinking are the main risk factors of MS progression. Regular MS surveillance and behavioral interventions are recommended for pre-elderly people with healthy obese phenotype.
Assuntos
Síndrome Metabólica/epidemiologia , Obesidade , Consumo de Bebidas Alcoólicas , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal , Fenótipo , Fatores de Risco , FumarRESUMO
The authors describe a fluorescent "turn-on" assay for detection of uric acid (UA) based on the use of graphene quantum dots coated with a shell of silver (GQD@Ag). The fluorescence of the GQDs is quenched by the silver shell. However, if the silver shell was removed via etching with H2O2 (which is produced by uricase catalyzed oxidation of UA), the fluorescence of the GQDs is restored. The resulting increase in fluorescence at 466 nm depends directly on the concentration of H2O2, which, in turn, depends on the concentration of UA. The method allows UA to be quantitated with a 2 µM detection limit. It was applied to the analysis of human urine samples and exhibited satisfactory results. The method is cost-effective, sensitive and selective for UA. In our perception, it provides a useful tool in clinical analysis and may be extended to other assays based on the use of oxidases. Graphical abstract Schematic of the reduction of Ag(I) and the growth of a silver shell on the surface of graphene quantum dots (GQDs) to form a GQD@Ag nanocomposite whose fluorescence is quenched. Uricase catalyzes the oxidation of uric acid (UA) to produce allantoin and H2O2 which etches the silver shell. This results in the release of GQDs and increased fluorescence, allowing quantitative analysis of UA.
RESUMO
OBJECTIVES: To investigate the association between obesity and osteoporosis in men aged above 50 in Chengdu. METHODS: Male participants aged above 50 were recruited from those who visited West China Hospital of Sichuan University for health examinations. Bone mineral density was measured by MetriScan Bone Densitometry. The participants were divided into three groups according to T values: normal, osteopenia and osteoporosis. RESULTS: About 5.75% (525 cases) of the 9 135 male participants had osteoporosis. The three groups had significant different anthropometric parameters, including body mass, waist circumference, hip circumference, body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHtR), a body shape index (ABSI), and body roundness index (BRI)( P<0.01). The participants with the highest quartile (Q4) of BMI, BRI, WHtR, WHR, ABSI, waist circumference and height had an age-adjusted odds ratios (OR) of 0.443 [95% confidence interval ( CI): 0.342-0.574), 0.580 (95% CI: 0.454-0.740), 0.587 (95% CI: 0.460-0.751), 0.664 (95% CI: 0.516-0.854], 1.369 (95% CI: 1.069-1.751), 0.634 (95% CI: 0.497-0.809), and 1.357 (95% CI: 1.047-1.758), respectively, for osteoporosis compared with those with the lowest quartile (Q1). The area under cures (AUC) of receiver operator characteristic (ROC) curve of BMI for osteoporosis was 0.606 (95% CI:0.580-0.632). CONCLUSIONS: Large body mass was negatively associated with osteoporosis in middle and old aged men. BMI is the strongest predictor of osteoporosis. Further longitudinal studies are required to verify such asscoiations.