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1.
Exp Ther Med ; 23(1): 43, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34849158

RESUMO

Hearing loss is a common sensory disorder that is mainly caused by the loss of hair cells (HCs). Drug-induced deafness, for which there is currently no effective treatment, is mainly caused by the inappropriate use of aminoglycoside antibiotics. Fasudil (Fas), a novel isoquinoline sulfonamide derivative, has exhibited antioxidant abilities in a number of previous studies. The aim of the present study was to investigate the potential effects of Fas against neomycin (Neo)-induced hair cell damage and elucidate the underlying mechanism. Flow cytometry and western blot analysis were used to detect the effects of Fas on cell apoptosis and to determine the expression levels of autophagy-related proteins, LC3B and Beclin 1, induced by Neo. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were detected using fluorescent probes. The effect of Fas on Neo-induced hair cell injury marker, GFP-LC3B, was also examined using the immunofluorescence technique. Fas was found to inhibit Neo-induced mitochondrial autophagy and mitochondrial membrane potential decline, in addition to reducing ROS levels and cell apoptosis caused by Neo treatment. However, Fas failed to inhibit the Neo-induced these above changes in cells with NDP52 overexpression. The putative binding sites of microRNA (miR)-489 on the 3'-untranslated region of nuclear dot protein 52 (NDP52) were predicted using the TargetScan 7.0 online tool, and this association was further verified using a dual-luciferase reporter assay. Moreover, the expression of miR-489 negatively regulated the expression of NDP52. Fas and miR-489 mimic inhibited the Neo-induced mitochondrial autophagy and mitochondrial membrane potential decline, in addition to reducing ROS levels and cell apoptosis. Knockdown of miR-489 expression using a miR-489 inhibitor blocked the inhibitory effects of Fas on the mitochondrial membrane potential, cell apoptosis and ROS production. Therefore, Fas may upregulate the expression of miR-489 to negatively regulate the expression of NDP52 at the post-transcriptional level, which in turn inhibits the activation of mitophagy and cell injury induced by Neo. Thus, Fas may act as a novel therapeutic option in the clinical treatment of hearing loss in the future.

2.
Bioorg Chem ; 119: 105516, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34856444

RESUMO

Both ruthenium (Ru) and isoquinoline (IQ) compounds are regarded as potential anticancer drug candidates. Here, we report the synthesis and characterization of three novel cyclometalated Ru(II)-isoquinoline complexes: RuIQ-3, RuIQ-4, and RuIQ-5, and evaluation of their in vitro cytotoxicities against a panel of cell lines including A549/DDP, a cisplatin-resistant human lung cancer cell line. A549/DDP 3D multicellular tumor spheroids (MCTSs) were also used to detect the drug resistance reversal effect of Ru(II)-IQ complexes. Our results indicated that the cytotoxic activities against cancer cells of Ru(II)-IQ complexes, especially RuIQ-5, were superior compared with cisplatin. In addition, RuIQ-5 exhibited low toxicity towards both normal HBE cells in vitro and zebrafish embryos in vivo. Further investigation on cellular mechanism of action indicated that after absorption by A549/DDP cells, RuIQ-5 was mainly distributed in the nucleus, which is different from cisplatin. Besides, RuIQ-5 could induce apoptosis through mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, ROS-mediated DNA damage, and cycle arrest at both S and G2/M phases. Moreover, RuIQ-5 could inhibit the overexpression of Nrf2 through regulation of Akt/GSK-3ß/Fyn signaling pathway and hindering the nuclear translocation of Nrf2. Based on these findings, we firmly believe that the studied Ru(II)-IQ complexes hold great promise as anticancer therapeutics with high effectiveness and low toxicity.

3.
Nanotechnology ; 33(6)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34710863

RESUMO

We propose an updated design on concentrated thermionic emission solar cells, which demonstrates a high solar-to-electricity energy conversion efficiency larger than 10% under 600 suns, by harnessing the exceptional electrical, thermal, and radiative properties of the graphene as a collector electrode. By constructing an analytical model that explicitly takes into account the non-Richardson behavior of the thermionic emission current from graphene, space charge effect in vacuum gap, and the various irreversible energy losses within the subcomponents, we perform detailed characterizations on the conversion efficiency limit and parametric optimum design of the proposed system. Under 800 suns, a maximum efficiency of 12.8% has been revealed, where current density is 3.87 A cm-2, output voltage is 1.76 V, emitter temperature is 1707 K, and collector temperature is 352 K. Moreover, we systematically compare the peak efficiencies of various configurations combining diamond or graphene, and show that utilizing diamond films as an emitter and graphene as a collector offers the highest conversion efficiency, thus revealing the important role of graphene in achieving high-performance thermionic emission solar cells. This work thus opens up new avenues to advance the efficiency limit of thermionic solar energy conversion and the development of next-generation novel-nanomaterial-based solar energy harvesting technology.

4.
J Biol Inorg Chem ; 26(7): 793-808, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34459988

RESUMO

Two new cyclometalated Ru(II)-ß-carboline complexes, [Ru(dmb)2(Cl-Ph-ßC)](PF6) (dmb = 4,4'-dimethyl-2,2'-bipyridine; Cl-Ph-ßC = Cl-phenyl-9H-pyrido[3,4-b]indole; RußC-3) and [Ru(bpy)2(Cl-Ph-ßC)](PF6) (bpy = 2,2'-bipyridine; RußC-4) were synthesized and characterized. The Ru(II) complexes display high cytotoxicity against HeLa cells, the stabilized human cervical cancer cell, with IC50 values of 3.2 ± 0.4 µM (RußC-3) and 4.1 ± 0.6 µM (RußC-4), which were considerably lower than that of non-cyclometalated Ru(II)-ß-carboline complex [Ru(bpy)2(1-Py-ßC)] (PF6)2 (61.2 ± 3.9 µM) by 19- and 15-folds, respectively. The mechanism studies indicated that both Ru(II) complexes could significantly inhibit HeLa cell migration and invasion, and effectively induce G0/G1 cell cycle arrest. The new Ru(II) complexes could also trigger apoptosis through activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP), and inducing cytochrome c release from mitochondria. Further research revealed that RußC-3 could deactivate the ERK/Akt signaling pathway thus inhibiting HeLa cell invasion and migration, and inducing apoptosis. In addition, RußC-3-induced apoptosis in HeLa cells was closely associated with the increase of intracellular ROS levels, which may act as upstream factors to regulate ERK and Akt pathways. More importantly, RußC-3 exhibited low toxicity on both normal BEAS-2B cells in vitro and zebrafish embryos in vivo. Consequently, the developed Ru(II) complexes have great potential on developing novel low-toxic anticancer drugs.

5.
Phys Rev E ; 103(6-1): 062136, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34271693

RESUMO

Numerous nanoscale studies that are related to harnessing photon energy focus on quantum effects. Thermodynamics analyses indicate the occurrence of a paradox for the standard model of the photocell with the power generated by a decay process. In order to measure the power accurately, a light-harvesting system connecting to Fermi contacts is proposed. Results show that the interference effect between different transition channels plays a decisive role in enhancing the power output of a photocell. The proposed model may provide a foundation for the future development of photoelectric converters.

6.
Mar Environ Res ; 167: 105295, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33714106

RESUMO

Marine biota, especially commercially important species, serves as a basis for human nutrition. However, millions of tons of plastic litter are produced and enter the marine environment every year, with potential adverse impacts on marine organisms. In the present study, we investigated the occurrence and characteristics of microplastic (MP) pollution in the digestive tracts of 13 species of wild nektons from 20 stations sampled in the South China Sea (SCS) and the Indian Ocean (IO), and assessed the human health risks of MPs. The detection rate of MPs ranged from 0.00% to 50.00% from the SCS, which was dramatically lower than that from the IO (10.00-80.00%). The average abundance of MP was 0.18 ± 0.06 items g wet weight-1 (ww-1) in the SCS, which was significantly lower than that in the IO with a concentration of 0.70 ± 0.16 items g ww-1. Most MPs were fibers in type, black in color, and polyester (PES) in polymer composition in both the SCS and IO. Interestingly, distinct profiles of MP pollution were found between the benthic and pelagic nektons: 1) The predominant MP composition was PES in the benthic nektons, whereas polyamide (PA) accounted for a larger part of the total MP count in the pelagic nektons within the SCS; 2) The abundance of MP in the benthic nektons (0.52 ± 0.24 items individual-1) was higher than that in the pelagic nektons (0.30 ± 0.11 items individual-1). Accordingly, the mean hazard score of MPs detected in the benthic nektons (220.66 ± 210.75) was higher than that in the pelagic nektons (49.53 ± 22.87); 3) The mean size of the MP in the pelagic nektons (0.84 ± 0.17 mm) was larger than that in the benthic nektons (0.49 ± 0.09 mm). Our findings highlight the need to further investigate the ecological impacts of MPs on wild nekton, especially commercially important species, and its potential implications for human health.


Assuntos
Microplásticos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Humanos , Oceano Índico , Plásticos , Poluentes Químicos da Água/análise
7.
Mar Pollut Bull ; 163: 111931, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33418343

RESUMO

Endocrine disrupting compounds (EDCs) in marine environments has become a major environmental concern. Nonetheless, the biological effects of EDCs on organisms in coastal environments remain poorly characterized. In this study, biomonitoring of EDCs in male fish Sebastiscus marmoratus was carried out in the Maowei Sea, China. The results showed that the concentration of 4-nonylphenol (4-NP) was below the detection limit, the concentrations of 4-tert-octylphenol (4-t-OP) and bisphenol A (BPA) in seawater were moderate compared with those in other global regions, and the possible sources are the municipal wastewater discharge. Nested ANOVA analyses suggest significant differences of the brain aromatase activities and plasma vitellogenin (VTG) expression between the port area and the oyster farming area. A new fish expert system (FES) was developed for evaluating the biological effects of EDCs on fish. Our findings show that the FES is a potential tool to evaluate the biological effects of marine pollutants.


Assuntos
Disruptores Endócrinos , Perciformes , Poluentes Químicos da Água , Animais , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/toxicidade , China , Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Monitoramento Ambiental , Masculino , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
8.
Environ Res ; 192: 110326, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068580

RESUMO

Microplastics (MPs) in the Arctic have raised increasing concern, but knowledge on MP contamination in benthic organisms from Arctic shelf regions, e.g., the Chukchi Sea is still limited. Therefore, the present study investigated the occurrence, characteristics, sources, and environmental implications of MPs in the three most common benthic species, namely sea anemone (Actiniidae und.), deposit-feeding starfish (Ctenodiscus crispatus), and snow crab (Chionoecetes opilio), from the Chukchi Sea. The abundances of MPs in the three benthic species were significantly greater than those from the Bering Sea, but lower than those from other regions globally. The top three compositions of MPs in the three species were polyester, nylon, and polyethylene terephthalate. The detection limit for MP size in the present study was 0.03 mm and the mean size of MP in the three species was 0.89 ± 0.06 mm. The surfaces of MPs found in the starfish and crabs were covered with many attachments, cracks, and hollows, while the surfaces of MPs found in the sea anemones were smooth, which was likely a consequence of different feeding behaviors. There was a significantly positive correlation between the abundances of MPs and other anthropogenic substances. The mean MP abundances in the sea anemones ranged from 0.2 items/individual to 1.7 items/individual, which was significantly higher than that in the deposit-feeding starfish (0.1-1.4 items/individual) and snow crabs (0.0-0.6 items/individual). Sea anemones inhabiting lower latitudes ingested relatively higher levels of MPs than those inhabiting higher latitudes. The MP abundances in the sea anemones are significantly and positively correlated with the seasonal reduced ratio of sea ice coverage from August to September. Our findings indicate that sea anemones could function as a bioindicator of MP pollution, and that the MPs in the benthos from the Chukchi Sea might originate from the melting sea ice, fishery activities and ocean currents.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Regiões Árticas , Monitoramento Ambiental , Plásticos , Poluentes Químicos da Água/análise
9.
Opt Lett ; 45(21): 5929-5932, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137035

RESUMO

Energy harvesting using thermoradiative systems has been extensively explored in recent years as a novel strategy for further reducing our energy footprint. However, the nighttime application, thermodynamic limit, and optimal design of such a system remain largely unaddressed so far. Here we propose an improved nighttime thermoradiative system (NTS) for electrical power generation by optically coupling Earth's surface with outer space. Our theoretical model predicts that the NTS operating with Earth (deep space) at 300 K (3 K) yields a maximum power density of 12.3Wm-2 with an efficiency limit of 18.5%, which is potentially more advantageous than previous nighttime energy harvesting systems, such as a nighttime thermoelectric generator. We find that optimizing the thickness of the active layer, enhancing thermal infrared emission, and employing a silver backreflector for photon recycling are crucially important in improving system performance. This Letter provides new insights for the optimal designs of NTSs and paves the way toward practical nighttime power generation.

10.
Bioinorg Chem Appl ; 2020: 8890950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879623

RESUMO

Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.

11.
Eur J Med Chem ; 203: 112562, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32698112

RESUMO

Two novel cyclometalated Ru(II) complexes containing isoquinoline ligand, [Ru(bpy)2(1-Ph-IQ)](PF6), (bpy = 2,2'-bipyridine; 1-Ph-IQ = 1-phenylisoquinoline; RuIQ-1) and [Ru(phen)2(1-Ph-IQ)](PF6) (phen = 1,10-phenanthroline; RuIQ-2) were found to show high cytotoxic activity against NCI-H460, A549, HeLa and MCF-7 cell lines. Notably, both of them exhibited IC50 values that were an order of magnitude lower than those of clinical cisplatin and two structurally similar Ru(II)-isoquinoline complexes [Ru(bpy)2(1-Py-IQ)](PF6)2 (Ru3) and [Ru(phen)2(1-Py-IQ)](PF6)2 (Ru4) (1-Py-IQ = 1-pyridine-2-yl). The cellular uptake and intracellular localization displayed that the two cyclometalated Ru(II) complexes entered NCI-H460 cancer cells dominantly via endocytosis pathway, and preferentially distributed in the nucleus. Further investigations on the apoptosis-inducing mechanisms of RuIQ-1 and RuIQ-2 revealed that the two complexes could cause S, G2/M double-cycle arrest by regulating cell cycle related proteins. The two complexes also could reduce the mitochondrial membrane potential (MMP), promote the generation of intracellular ROS and trigger DNA damage, and then lead to apoptosis-mediated cell death. More importantly, RuIQ-2 exhibits low toxicity both towards normal HBE cells in vitro and zebrafish embryos in vivo. Accordingly, the developed complexes hold great potential to be developed as novel therapeutics for effective and low-toxic cancer treatment.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Isoquinolinas/química , Rutênio/química , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Transporte Biológico , Linhagem Celular Tumoral , Técnicas de Química Sintética , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Humanos , Ligantes , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Peixe-Zebra
12.
Acta Biomater ; 113: 541-553, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32562802

RESUMO

Cancer therapeutics are varied and target diverse processes in cancer progression. Photodynamic therapy (PDT), photothermal therapy (PTT), and the inhibition of pro-cancer proteases are non-invasive anticancer therapeutics that attract increasing attentions for their enhanced specificities and milder systemic toxicities compared to traditional therapeutics. These modalities offer advantages to compensate for the shortcomings of their counterparts. For instance, PDT or PTT efficiently eliminates locally confined tumor cells while exhibiting no effect on metastatic tumor cells. In contrast, the inhibition of pro-cancer proteases systemically suppresses the proliferation and metastasis of cancer cells but does not eradicate existing cancer cells. To synergize these therapeutics, we hereby report a versatile nanoparticle that integrates the effects of PDT, PTT, and enzyme-inhibition. This nanoparticle (CIKP-NP) was synthesized by covalently or non-covalently modifying a photothermal nanoparticle with a photosensitizer, a pro-cancer protease inhibitor, and an albumin-binding molecule. After confirming the PDT, PTT, albumin-binding, and enzyme-inhibition properties at the molecular level, we demonstrated that CIKP-NP killed tumor cells through PDT or PTT and suppressed tumor cell invasion through enzyme-inhibition. In addition, through a breast cancer xenograft mouse model, we demonstrated that CIKP-NP suppressed tumor growth by PDT or PTT effect. Notably, the synergism of PDT and PTT significantly enhanced its anticancer efficiency. Furthermore, CIKP-NP significantly suppressed cancer metastasis in a lung metastatic mouse model. Last, biodistribution and the in vivo retention of CIKP-NP confirmed the tumor-targeting property. Beyond demonstrating the anti-tumor and anti-metastatic efficacy of CIKP-NP, our study also suggests a new strategy to synergize multiple anticancer therapeutics.


Assuntos
Neoplasias , Fotoquimioterapia , Animais , Proliferação de Células , Ouro , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Distribuição Tecidual
13.
Mar Pollut Bull ; 158: 111349, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32573451

RESUMO

Microplastic (MP) pollution is an emerging contaminant in aquatic environments worldwide. Nonetheless, the developmental toxicity of MPs in the early life stages of fish and the mechanisms involved are not yet fully understood. The present study investigated the effects of different concentrations of polystyrene (PS) MPs on the early development of the marine model fish the medaka Oryzias melastigma. Our results showed that waterborne exposure to PS MPs significantly delayed the hatching time, altered the heartbeat and decreased the hatching rate of embryos. Furthermore, the genes involved in cardiac development, encoding for embryo-hatching enzymes, as well as inflammatory responses were significantly upregulated. The transcriptome results showed that mainly the pathways involved in metabolism, immune response, genetic information processing and diseases were significantly enriched. These results demonstrate that PS MPs negatively impact embryogenesis and the immune response of O. melastigma.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Desenvolvimento Embrionário , Microplásticos , Plásticos
14.
Ecotoxicol Environ Saf ; 192: 110271, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32044605

RESUMO

Pollution with total petroleum hydrocarbons (TPHs) is a global concern and particularly in coastal environments. Polycyclic aromatic hydrocarbons (PAHs) are regarded as the most toxic components of TPHs and they can also be derived from other sources. Fangcheng Port is considered as a representative emerging coastal city in China, but the status, sources, and hazards to organisms and humans with respect to contamination with PAHs and TPHs are unknown in the coastal regions of this area. Therefore, in this study, we cloned cytochrome P450 family genes (CYP1A1, CYP3A, and CYP4) and heat shock protein 70 gene (HSP70) in the clam Meretrix meretrix as well as optimizing the method for measuring the 7-ethoxyresorufin O-deethylase activity. These molecular indicators and four specific physiological indexes were found to be appropriate biomarkers for indicating the harmful effects of PAHs and TPHs on clams after exposure to the crude oil water-soluble fraction. In field monitoring surveys, we found that the 2- and 3-ring PAHs were dominant in the clams whereas the 4- to 6-ring PAHs were dominant in the sediments at each site. The PAH levels (3.63-12.77 ng/g wet weight) in wild clams were lower, whereas the TPH levels (13.25-70.50 µg/g wet weight) were higher compared with those determined previous in China and elsewhere. The concentrations of PAHs and TPHs in the sediments (19.20-4215.76 ng/g and 3.65-866.40 µg/g dry weight) were moderate compared with those in other global regions. Diagnostic ratio analysis demonstrated that the PAHs were derived mainly from pyrogenic sources. The TPHs may have come primarily from industrial effluents, land and maritime transportation, or fishing activities. The Integrated Biomarker Response version 2 indexes indicated that the clams collected from site S5 exhibited the most harmful effects due to contamination by PAHs and TPHs. Human health risk assessments demonstrated that the risks due to PAHs and TPHs following the consumption of clams can be considered acceptable. Our results suggest that continuous monitoring of contamination by PAHs and TPHs is recommended in this emerging coastal city as well as assessing their human health risks.


Assuntos
Monitoramento Biológico/métodos , Bivalves/efeitos dos fármacos , Biomarcadores Ambientais/efeitos dos fármacos , Sedimentos Geológicos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Animais , Bivalves/metabolismo , China , Cidades , Humanos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Urbanização , Poluentes Químicos da Água/metabolismo
15.
J Mater Chem B ; 8(3): 504-514, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31840729

RESUMO

Inhibition of pro-cancer proteases is a potent anticancer strategy. However, protease inhibitors are mostly developed in the forms of small molecules or peptides, which normally suffer from insufficient metabolic stability. The fast clearance significantly impairs the antitumor effects of these inhibitors. In this study, we report a nanometer-sized inhibitor of a pro-cancer protease, suppressor of tumorigenicity 14 (st14), which has been reported as a potent prognostic marker for multiple cancers. This st14 inhibitor was fabricated by conjugating a recombinant st14 inhibitor (KD1) with carbon quantum dots (CQDs). CQD-KD1 not only demonstrated high potency of inhibiting st14 activity in biochemical experiments, but also remarkably suppressed the invasion of breast cancer cells. In contrast to the original recombinant KD1, CQD-KD1 demonstrated a prolonged retention time in plasma and at the tumor site because of the reduced renal clearance. Consistently, CQD-KD1 demonstrated enhanced efficacies of suppressing tumor growth and cancer metastases in vivo. In addition, CQD-KD1 precisely imaged tumor tissues in cancer-grafted mice by specifically targeting the over-expressed st14 on the tumor cell surface, which indicates CQD-KD1 as a potent probe for the fluorescence guided surgery of tumor resection. In conclusion, this study demonstrates that CQD-KD1 is a highly potent diagnostic and therapeutic agent for cancer treatments.


Assuntos
Antineoplásicos/farmacologia , Aprotinina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proteínas Recombinantes/farmacologia , Serina Endopeptidases/metabolismo , Animais , Antineoplásicos/química , Aprotinina/química , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Carbono/química , Feminino , Humanos , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Pontos Quânticos/química , Proteínas Recombinantes/química , Propriedades de Superfície , Células Tumorais Cultivadas
16.
Int J Nanomedicine ; 14: 6799-6812, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692522

RESUMO

Background: Photodynamic therapy (PDT), a clinical anticancer therapeutic modality, has a long history in clinical cancer treatments since the 1970s. However, PDT has not been widely used largely because of metabolic problems and off-target phototoxicities of the current clinical photosensitizers. Purpose: The objective of the study is to develop a high-efficiency and high-specificity carrier to precisely deliver photosensitizers to tumor sites, aiming at addressing metabolic problems, as well as the systemic damages current clinical photosensitizers are known to cause. Methods: We synthesized a polydopamine (PDA)-based carrier with the modification of folic acid (FA), which is to target the overexpressed folate receptors on tumor surfaces. We used this carrier to load a cationic phthalocyanine-type photosensitizer (Pc) and generated a PDA-FA-Pc nanomedicine. We determined the antitumor effects and the specificity to tumor cell lines in vitro. In addition, we established human cancer-xenografted mice models to evaluate the tumor-targeting property and anticancer efficacies in vivo. Results: Our PDA-FA-Pc nanomedicine demonstrated a high stability in normal physiological conditions, however, could specifically release photosensitizers in acidic conditions, eg, tumor microenvironment and lysosomes in cancer cells. Additionally, PDA-FA-Pc nanomedicine demonstrated a much higher cellular uptake and phototoxicity in cancer cell lines than in healthy cell lines. Moreover, the in vivo imaging data indicated excellent tumor-targeting properties of PDA-FA-Pc nanomedicine in human cancer-xenografted mice. Lastly, PDA-FA-Pc nanomedicine was found to significantly suppress tumor growth within two human cancer-xenografted mice models. Conclusion: Our current study not only demonstrates PDA-FA-Pc nanomedicine as a highly potent and specific anticancer agent, but also suggests a strategy to address the metabolic and specificity problems of clinical photosensitizers.


Assuntos
Ácido Fólico/farmacologia , Indóis/farmacologia , Nanopartículas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polímeros/farmacologia , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Estabilidade de Medicamentos , Feminino , Ácido Fólico/química , Células HeLa , Humanos , Indóis/química , Células MCF-7 , Camundongos , Nanomedicina , Nanopartículas/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Polímeros/química , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Phys Rev E ; 99(6-1): 062123, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31330757

RESUMO

We study the performance of a thermal management device with small scales by considering a strong coupling between quantum qubits. A small change of the thermal current at the base will cause a great change to the thermal current at the emitter and collector, reaching its promise for large thermal amplification. The competition between the quantum coherence and the incoherence induces a significant variation in the amplification factor and consequently relates the thermal controls with quantum effects. The results obtained here will provide a feasible scheme for the realization of quantum thermal management devices.

18.
Theranostics ; 9(3): 884-899, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809315

RESUMO

Cancer cell expresses abundant surface receptors. These receptors are important targets for cancer treatment and imaging applications. Our goal here is to develop nanoparticles with cargo loading and tumor targeting capability. Methods: A peptide targeting at cancer cell surface receptor (urokinase receptor, uPAR) was expressed in fusion with albumin (diameter of ~7 nm), and the fusion protein was assembled into nanoparticles with diameter of 40 nm, either in the presence or absence of cargo molecules, by a novel preparation method. An important feature of this method is that the nanoparticles were stabilized by hydrophobic interaction of the fusion protein and no covalent linking agent was used in the preparation. The stability, the cargo release, in vitro and in vivo properties of such formed nanoparticles were characterized by transmission electron microscopy, dynamic light scattering, gel shift assay, laser scanning confocal microscopy and 3D fluorescent molecular tomography. Results: The nanoparticles were stable for more than two weeks in aqueous buffer, even in the buffer containing 10% fetal bovine serum. Interestingly, in the presence of urokinase receptor, the uPAR-targeting nanoparticle disintegrated into 7.5 nm fragments and released its cargo, but not the non-targeting nanoparticles made from albumin by the same preparation method. Such nanoparticles also showed higher uptake and cytotoxicity to the receptor-expressing cancer cells in vitro and higher tumor accumulation in xenografted tumor-bearing mice in vivo compared to the non-targeting nanoparticles. Conclusion: Our results demonstrate a new function of cell surface receptor as a responsive trigger to disassemble nanoparticles, besides its common use to enrich targeting agents. Such nanoparticles were thus named receptor-responsive nanoparticles (RRNP).


Assuntos
Carcinoma Hepatocelular/terapia , Portadores de Fármacos/administração & dosagem , Terapia de Alvo Molecular/métodos , Nanopartículas/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Camundongos , Transplante de Neoplasias , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Ligação Proteica , Transplante Heterólogo , Resultado do Tratamento
19.
J Inorg Biochem ; 193: 112-123, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711557

RESUMO

Thioredoxin reductase (TrxR), a major component of the thioredoxin system, makes a critical role in regulating cellular redox signaling and is found to be overexpressed in many human cancer cells. TrxR has become an attractive target for anticancer agents. In this work, three Ru(II) complexes with salicylate as ligand, [Ru(phen)2(SA)] (phen = 1,10-phenanthroline, SA = salicylate, 1), [Ru(dmb)2(SA)] (dmb = 4,4'-dimethyl-2,2'-bipyridine, 2) and [Ru(bpy)2(SA)] (bpy = 2,2'-bipyridine, 3), were synthesized and characterized. The anticancer effect exerted by them was evaluated. Complex 1 was found to exhibit obvious anticancer activity, in comparison with cisplatin, against cancer cell lines, while displaying low toxicity to the normal cell line BEAS-2B. The mechanism of complex 1 cancer cell growth suppress was investigated in A549 cells. Complex 1 exerted its anticancer through inducing apoptosis and triggering cell cycle arrest at the G0/G1 phase. Complex 1 can selectively inhibit TrxR activity and thus promote the generation and accumulation of reactive oxygen species (ROS), which subsequently trigger mitochondrial dysfunction and DNA damage, activate oxidative stress-sensitive mitogen activated protein kinase (MAPK), and suppress the protein kinase B (PKB or AKT) signal pathway, resulting in apoptosis in A549 cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Salicilatos/farmacologia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Dano ao DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/toxicidade , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Rutênio/química , Salicilatos/síntese química , Salicilatos/toxicidade , Transdução de Sinais/efeitos dos fármacos
20.
J Inorg Biochem ; 189: 192-198, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30317065

RESUMO

Antimicrobial photodynamic therapy (aPDT) is an effective way to combat infectious diseases and antibiotic resistance. Photosensitizer is a key factor of aPDT and has triggered extensive research interest. In this study, a new asymmetric Zn(II) phthalocyanine mono-substituted with a triazatricyclodecane moiety (compound 3) and its cationic N-methylated derivative (compound 4) were synthesized. Their photodynamic antimicrobial activities were evaluated using bioluminescent bacterial strains. Compound 3 showed phototoxicity only toward the Gram-positive bacteria, whereas the cationic derivative compound 4 exhibited strong anti-bacterial activity against both Gram-positive and Gram-negative strains. These bacterial species were eradicated (>4.0 logs or 99.99% killing) at appropriate concentrations of compound 4 with 12.7 J/cm2 of red light, demonstrating compound 4 as a potent aPDT agent.


Assuntos
Indóis/química , Fármacos Fotossensibilizantes/química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Fotoquimioterapia
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