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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 120028, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119768

RESUMO

A novel visual nanoprobe was developed for the sequential detection of morin and zinc ion (Zn2+) based on Cl and N co-doped carbon quantum dots (ClNCQDs) via a fluorometric and colorimetric dual-readout mode. The yellow fluorescence ClNCQDs was synthesized by the one-step hydrothermal treatment of o-chlorobenzoic acid and p-phenylenediamine. The most distinctive property of the ClNCQDs is the large stokes shift (177 nm), which is significantly higher than other reported CQDs. The fluorescence of the ClNCQDs can be effectively quenched by morin based on the synergistic effect of IFE, electrostatic interaction, and dynamic quenching process, and recovered upon the addition of Zn2+ due to strong interaction between morin and Zn2+. The nanoprobe exhibited favorable selectivity and sensitivity toward morin and Zn2+ with detection limits of 0.09 µM and 0.17 µM, respectively. Simultaneously, the color of the ClNCQDs solution was changed (light-pink â†’ faint-yellow â†’ dark-yellow) along with the variation of the fluorescence signal of the ClNCQDs. This proposed nanoprobe was successfully applied for morin and Zn2+ analyses in actual samples and live cells with high accuracy. The results of this study demonstrate the great application prospects of the ClNCQDs for morin and Zn2+ detection in complex actual samples and biosystems.


Assuntos
Pontos Quânticos , Carbono , Colorimetria , Flavonoides , Limite de Detecção , Zinco
2.
Mikrochim Acta ; 188(6): 183, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33970343

RESUMO

Carbon dots (CDs) are a rising star in the field of cellular imaging, especially cytoplasmic imaging, attributing to the super-stable optical performance and ultra-low biological toxicity. Nucleolus can accurately reflect the expression state of a cell and is strongly linked to the occurrence and development of many diseases, so exploring bran-new CDs for nucleolus-orientation imaging with no-wash technology has important theoretical value and practical significance. Herein, nitrogen-doped carbon dots (N-CDs) with green fluorescence (the relative fluorescence quantum yield of 24.4%) was fabricated by the hydrothermal treatment of m-phenylenediamine and p-aminobenzoic acid. The N-CDs possess small size, bright green fluorescence, abundant surface functional groups, excellent fluorescence stability and good biocompatibility, facilitating that the N-CDs are an excellent imaging reagent for cellular imaging. N-CDs can particularly bind to RNA in nucleoli to enhance their fluorescence, which ensures that the N-CDs can be used in nucleolus-orientation imaging with high specificity and wash-free technique. This study demonstrates that the N-CDs have a significant feasibility to be used for nucleolus-orientation imaging in biomedical analysis and clinical diagnostic applications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33684336

RESUMO

A high-efficiency spectrophotometric method based on nitrogen-doped fluorescent carbon dots (N-FCDs) was developed for the ultrasensitive determination of carmine (CRM) in foodstuffs. The N-FCDs were fabricated via a one-pot hydrothermal method with m-phenylenediamine as the starting material. The detection principle was based on the fluorescence quenching effect of N-FCDs by CRM, where their interaction was due to the inner filter effect (IFE) and static quenching. A good linear relationship was established for CRM detection in a concentration range of 0.1-10.0 µM with a detection limit as low as 11.2 nM. The proposed method achieved satisfactory results for CRM determination in commercial food products with recoveries better than 98.6% and relative standard deviations (RSDs) less than 4.07%. The method established in this study was simple, ultrasensitive and reliable for rapid detecting CRM in a food matrix, which could be potentially used as a useful sensing agent for the analysis of additive food colourants.


Assuntos
Carbono/química , Carmim/análise , Corantes Fluorescentes/química , Análise de Alimentos , Contaminação de Alimentos/análise , Pontos Quânticos/química , Espectrometria de Fluorescência
5.
Biomater Sci ; 9(6): 2255-2261, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33533378

RESUMO

Intracellular pH and hypochlorite (ClO-) concentration play an important role in life activities, so there is an urgent need to develop a valid strategy to monitor pH and ClO- in biological systems with high sensitivity and specificity. In this study, we report long-wavelength emission nitrogen-doped carbon dots (N-CDs) and their potential applications in intracellular pH variation, ClO- sensing and cell imaging. The N-CDs were prepared via a facile one-pot hydrothermal method of neutral red (NR) and glutamine (Gln). N-CDs exhibited a pH-sensitive response in the range of 4.0-9.0 and a good linear relationship in the range of 5.6-7.4, which indicated that N-CDs are an ideal agent for monitoring pH fluctuations in living cells. In addition, ClO- was capable of reducing the photoluminescence of N-CDs based on static quenching. The linear range is 1.5-112.5 µM and 112.5-187.5 µM, and the LOD is 0.27 µM. Besides, the as-fabricated N-CDs have been smoothly achieved to monitor pH and ClO- in PC-12 living cells due to their great biocompatibility and lower cytotoxicity, demonstrating their promising applications in the biomedical field. Compared with other CD-based methods, the as-proposed N-CDs have a longer fluorescence emission, which makes them potentially valuable in biological systems. The results pave a way towards the construction of long-wavelength carbon-based nanomaterials for fluorescence sensing and cell imaging.


Assuntos
Carbono , Pontos Quânticos , Corantes Fluorescentes , Concentração de Íons de Hidrogênio , Ácido Hipocloroso , Nitrogênio
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119506, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33561684

RESUMO

Azithromycin (AZM)1 is one of the most widely used antibiotics. AZM abuse is easy to cause great harm to human body, so developing a rapid and sensitive method to detect AZM is of great importance. Herein, 3-aminothiophenol as only reaction precursor, nitrogen and sulfur co-doped carbon quantum dots (N,S-CQDs)2 were fabricated by one-step hydrothermal carbonization method. All characteristics demonstrate that N,S-CQDs possess good water solubility, high fluorescence stability and low cytotoxicity. Without being disturbed by amino acids and drugs, the most interesting finding is that AZM can efficiently quench the fluorescence of N,S-CQDs by a synergistic effect of electrostatic interaction and static quenching. A fluorescent probe for the detection of AZM was constructed with high selectivity and good sensitivity, achieving two linear ranges of 2.5-32.3 µM and 37.2-110 µM and a limit of detection of 0.76 µM. The proposed fluorescent method was used for the detection of AZM in cells with fulfilling results. More importantly, the fluorescent probe was successfully used to the detection of AZM in tablets and human urine with recovery rate and relative standard deviations of 98.2-104.8% and 0.04-3.46%, respectively, which was confirmed by the standard method of HPLC-UV. This finding illustrates the usefulness and feasibility of N,S-CQDs as an effective fluorescent probe for the detection of AZM in tablets and human urine, which is helpful for supervising and guiding pharmacy.


Assuntos
Pontos Quânticos , Azitromicina , Carbono , Humanos , Nitrogênio , Comprimidos
7.
Anal Bioanal Chem ; 413(5): 1485-1492, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33462660

RESUMO

In this work, an ultrasensitive sensing system based on fluorescent carbon dots (CDs) was developed for the tartrazine (Tar) determination. The CDs were prepared via a simple one-pot hydrothermal method with m-phenylenediamine as the only precursor. The physical and chemical properties were in detail characterized by transmission electron microscopy (TEM), MALDI-TOF MS, UV-vis absorption and photoluminescence (PL) spectroscopy, elemental analysis, and Fourier transform infrared spectroscopy (FTIR). Upon exposure to Tar, the fluorescence of CDs was efficiently quenched via the dynamic interaction between CDs and Tar as well as the inner filter effect (IFE). With this information, the CDs were proposed as a fluorescence probe for Tar detection. It was found that CDs had high sensitivity and selectivity for Tar sensing, and the linear relationship was observed in the range of 0.01-25.0 µM with the corresponding detection limit (3σ/k) of 12.4 nM, which is much more sensitive than any of the existed CD-based sensing platform. The investigated sensing system was finally utilized for Tar sensing in various food matrices with a high degree of accuracy. The spiked recoveries were in a range of 96.4-105.2%, and the relative standard deviations (RSDs) were lower than 4.13%. This work highlights the great application prospects of CDs for Tar sensing in a rapid, simple, and sensitive way.


Assuntos
Carbono/química , Análise de Alimentos/métodos , Corantes de Alimentos/análise , Nanopartículas/química , Tartrazina/análise , Corantes Fluorescentes/química , Limite de Detecção , Nanopartículas/ultraestrutura , Espectrometria de Fluorescência/métodos
8.
Mikrochim Acta ; 188(1): 16, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399925

RESUMO

Nitrogen, sulfur, phosphorus, and chlorine co-doped carbon nanodots (NSPCl-CNDs) were fabricated by acid-base neutralization and exothermic carbonization of glucose. The obtained NSPCl-CNDs possess excellent fluorescence properties and good biocompatibility. Curcumin (Cur) can dramatically quench the fluorescence of NSPCl-CNDs based on a synergistic effect of electrostatic interaction, inner filter effect, and static quenching, so a "turn-off" fluorescent probe for Cur detection was constructed with linear ranges of 0.24-13.16 µM and 13.62-57.79 µM. The LOD and LOQ of this fluorescent probe for Cur are 8.71 nM and 29.03 nM, respectively. More importantly, the fluorescence of the NSPCl-CNDs-Cur system can be recovered by europium ion (Eu3+), so a "turn-on" fluorescent probe for Eu3+ determination was established. The linear range, LOD, and LOQ for the detection of Eu3+ were 2.36-32.91 µΜ, 73.29 nM, and 244.30 nM, respectively. The proposed fluorescence methods were successfully utilized for Cur and Eu3+ determination in real samples with recoveries in the range 95.64-104.13% and 97.06-98.70%, respectively. Furthermore, the qualitative analysis of Cur can be realized by reagent strips with satisfying results. Finally, the as-constructed "off-on" fluorescent probe was successfully used to sequentially analyze Cur and Eu3+ at the cellular level. This method is simple and easy to implement, manifesting that NSPCl-CNDs have potential application value in fluorescent probing, food and drug testing, environmental monitoring, and cellular labeling. Graphical abstract.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119432, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33472136

RESUMO

In this work, the red emission multifunctional carbon dots (R-CDs) were prepared via one-pot hydrothermal strategy of neutral red (NR) and ethylenediamine (EDA) for the label-free detection of berberine and curcumin, cell imaging, and fluorescent flexible film. The as-fabricated R-CDs not only possess good water dispersibility and excellent fluorescence stability, but also were successfully employed as a photoluminescent nanoprobe for label-free monitoring of berberine (BRH) and curcumin (Cur) based on dynamic quenching and internal filter effect (IFE), respectively. More importantly, as-proposed R-CDs displayed outstanding cellular permeability and lower cytotoxicity for cellular applications, which was consistent with the results of confocal fluorescence imaging and cell viability measurement of SMMC7721 cells. Thus, the multifunctional R-CDs may provide a rich tool library for biosensing and cellular imaging reagent applications. Interestingly, R-CDs were also used to manufacture R-CDs/PVA composites as fluorescent flexible films. To the best of our knowledge, this is the first demonstration of a label-free multifunctional fluorescent nanoprobe for berberine and curcumin based on red emission CDs.


Assuntos
Berberina , Curcumina , Pontos Quânticos , Carbono , Corantes Fluorescentes , Espectrometria de Fluorescência
10.
Anal Chim Acta ; 1144: 1-13, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453785

RESUMO

The fluorescent sensor, especially ratiometric fluorescent sensor, is one of the most important applications for CQDs, which is becoming a research hotspot. Herein, carbon quantum dots co-doped with nitrogen, phosphorus and chlorine (NPCl-CQDs) were synthesized by acid-base neutralization reaction exothermic carbonization method. The as-fabricated NPCl-CQDs could emit blue fluorescence and possess excellent fluorescence properties. Based on the FRET, multifunctional and ratiometric fluorescent sensors for "on-off-on" sequential determination of riboflavin, Ag+, and Cys with good selectivity and high sensitivity were established. The linear range of riboflavin, Ag+, and Cys are 0.50-10.18 µM and 15.89-27.76 µM, 0.66-1.46 mM and 1.50-4.20 mM, and 0.01-0.15 µM and 0.15-0.36 µM with the limit of detection of 3.50 nM, 26.38 µM, and 0.96 nM, respectively. Furthermore, the sensors were successfully used to determine riboflavin, Ag+, and Cys in tablets, river water, and human urine with the recoveries of 95.2-104.0%, 95.6-102.0%, and 94.8-106.4%, respectively. More importantly, the as-constructed "on-off-on" NPCl-CQDs-based ratiometric fluorescent sensors were applied for detecting riboflavin, Ag+, and Cys in HeLa cells with satisfying results. The finding of this study shows the feasibility and effectiveness of the NPCl-CQDs as the available ratiometric fluorescent sensors for the determination of riboflavin, Ag+, and Cys in real samples and living cells.


Assuntos
Pontos Quânticos , Carbono , Cisteína , Células HeLa , Humanos , Riboflavina , Prata
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 247: 119085, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33161261

RESUMO

Many reports have suggested that near-infrared (NIR) fluorescent probes are one of the most promising molecules for improving the sensitivity of fluorescence sensing and imaging. Herein, gold nanoclusters with excellent near-infrared photoluminescence (PL) were synthesized by a simply hydrothermal treatment of hydrogen tetrachloroaurate(III) trihydrate and glutathione (GSH). The NIR PL of GSH-capped gold nanoclusters (GSH-AuNCs) can be significantly quenched by Fe3+, which follows a dynamic quenching mechanism. However, the NIR PL of the GSH-AuNCs/Fe3+ system can be recovered after the addition of ascorbic acid (AA). The decrease and increase of NIR PL intensities of GSH-AuNCs were linearly correlated with the concentration of Fe3+ and AA, respectively. Therefore, a turn-off-on NIR PL sensing strategy can be constructed for sequential detection of Fe3+ and AA with the linear range of 0.7-180 µM and 0.5-120 µM, respectively. The proposed NIR PL sensor exhibits excellent sensing performance and has been applied to the determination of Fe3+ and AA in real samples with satisfactory results.

12.
Int J Legal Med ; 135(3): 709-718, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32851473

RESUMO

The MiSeq® FGX Forensic system and the HID-Ion AmpliSeq Panel were previously developed for massively parallel sequencing (MPS) for forensic casework. Among the three major sequencing platforms, BGISEQ-500TM, which is based on multiple PCRs, is still lacking in forensics. Here, a novel forensic panel was constructed to detect 186 single-nucleotide polymorphisms (SNPs) and 123 short tandem repeats (STRs) with MPS technology on the BGISEQ-500™ platform. First, the library preparation, sequencing process, and data analysis were performed, focusing on the average depth of coverage and heterozygote balance. We calculated the allelic frequencies and forensic parameters of STR and SNP loci in 73 unrelated Chinese Han individuals. In addition, performance was evaluated with accuracy, uniformity, sensitivity, PCR inhibitor, repeatability and reproducibility, mixtures, degraded samples, case-type samples, and pedigree analyses. The results showed that 100% accurate and concordant genotypes can be obtained, and the loci with an abundance in the interquartile range accounted for 92.90% of the total, suggesting reliable uniformity in this panel. We obtained a locus detection rate that was higher than 98.78% from 78 pg of input DNA, and the optimal amount was 1.25-10 ng. The maximum concentrations of hematin and humic acid were 200 and 100 µM, respectively (the ratios of detected loci were 96.52% and 92.41%), in this panel. As a mixture, compared with those of SNPs, minor-contributor alleles of STRs could be detected at higher levels. For the degraded sample, the ratio of detected loci was 98.41%, and most profiles from case-type samples were not significantly different in abundance in our studies. As a whole, this panel showed high-performance, reliable, robust, repeatable, and reproducible results, which are sufficient for paternity testing, individual identification, and use for potentially degraded samples in forensic science.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Criança , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Gravidez , Reprodutibilidade dos Testes , Análise de Sequência de DNA/instrumentação
13.
Artigo em Inglês | MEDLINE | ID: mdl-33301365

RESUMO

An ultra-sensitive spectrofluorimetry method was developed and validated for the rapid determination of ferrocyanide ions (hexacyanidoferrate(II), FeCN6 4-, FCNs) by using sulphur (S) and nitrogen (N) dual-doped fluorescence carbon nanoparticles (S,N-FCNPs) as nanoprobe. The fluorescence of S,N-FCNPs was strongly reduced due to the dynamic interaction between S,N-FCNPs and FeCNs. The developed method proved to be highly sensitive and selective for FeCNs detection with linearity in three concentration ranges over four orders of magnitude, covering 0.01-200.0 µg/mL. A limit of detection (LOD) of 2.8 ng/mL was obtained. The method was successfully applied for the determination of FeCNs in a series of dietary food salt samples and gave satisfactory results; the spiked recoveries were 97.6‒104.6% with standard uncertainty less than 5.8%. The method proved to be applicable for ultra-trace detection of FeCNs in food salt samples, having advantages in great simplicity, rapid response, low cost, favourable selectivity, and high sensitivity.


Assuntos
Ferrocianetos/análise , Corantes Fluorescentes/química , Análise de Alimentos , Contaminação de Alimentos/análise , Nanopartículas/química , Carbono/química , Nitrogênio/química , Sais/química , Espectrometria de Fluorescência , Enxofre/química
14.
Mater Sci Eng C Mater Biol Appl ; 118: 111478, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33255057

RESUMO

The fluorescent boron, nitrogen and sulfur co-doped carbon dots (BNSCDs) were prepared by simple hydrothermal reaction of 4-carboxyphenylboronic acid and 2,5-diaminobenzenesulfonic acid at 200 °C for 8 h. The fluorescence of the BNSCDs could be quenched by Fe3+ based on the electron transfer between Fe3+ and BNSCDs, so a label-free, good selectivity and high sensitivity method for Fe3+determination was established with linear range and LOD of 1.5-692 µmol/L and 87 nmol/L, respectively. And then the fluorescent probe was employed for detection of Fe3+ in tap water, coal gangue, fly ash and food samples successfully. Moreover, the as-prepared BNSCDs could serve as a novel pH fluorescent probe in the range of pH 1.60-7.00, which could be attributed to the proton transfer of carboxyl groups on the surface of BNSCDs. More importantly, the pH fluorescent probe possesses fast, real-time and low toxicity, applying for intracellular pH fluorescence imaging in HIC, HIEC, LO2 and SMMC7721 cells. In view of its simplicity, timely response and outstanding compatibility, the as-fabricated BNSCDs show the potential applications in water quality and solid waste monitoring, food detection, real-time measuring of intracellular pH change in vitro.


Assuntos
Citrus sinensis , Pontos Quânticos , Boro , Carbono , Corantes Fluorescentes , Concentração de Íons de Hidrogênio , Nitrogênio , Espectrometria de Fluorescência , Enxofre
15.
Food Chem Toxicol ; 146: 111848, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33166671

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP), which is widely used as an industrial plasticizer, may cause liver damage. Concomitantly, bad dietary habits can exacerbate the liver burden. In this study, high-fat diet (HFD)-fed rats were treated with DEHP (10, 100, or 300 mg/kg bw) for 5 weeks, and a biochemical method was adopted to detect serum lipid contents. Key metabolic genes and pathological changes were assessed by different methods (RT-PCR, Western Bloting, ELISA and HE staining). The rats which were exposed to DEHP at a dose of 10 mg/kg bw exhibited dyslipidemia and increased transcription of SREBP-1 and its target FAS, thereby prompting de novo lipogenesis, but they did not become obese. Instead, DEHP at a dose of 300 mg/kg bw elevated the levels of AMPK phosphorylation and the mRNA levels of PPAR-α, PGC-1α, CPT-1 and lipin-1 in the liver, which led to fatty acid oxidation. Additionally, DEHP at the highest dose increased the TNF-α mRNA expression in the liver. Based on these findings, we conclude that excess fatty acid oxidation might increase the inflammatory response. No toxic effects on hepatic function were observed. These findings suggest that different doses of DEHP have the potential to disturb hepatic metabolic imbalance in HFD-fed rats.


Assuntos
Dietilexilftalato/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Proliferação de Células , Dieta Hiperlipídica , Ácidos Graxos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inflamação/induzido quimicamente , Masculino , Ratos , Ratos Wistar
16.
Immun Inflamm Dis ; 8(4): 695-703, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33017098

RESUMO

BACKGROUND: Graves' disease (GD) is a clinical autoimmune thyroid disease. During the treatment of GD, antithyroid drug-induced agranulocytosis (TIA) is a common and even life-threatening adverse drug reaction. Previous studies suggested that susceptibility to TIA is strongly associated with HLA-B*27:05, HLA-B*38:02, and HLA-DRB1*08:03 genetic variation and six single nucleotide polymorphisms (SNPs) in MICA genes. AIMS: The purpose of this study is to further study the associations between TIA, HLA-B and MICA. MATERIALS & METHODS: We genotyped MICA-STR and MICA-129 variants in 41 TIA and 308 control patients with GD and investigated the linkage effect among SNPs and short tandem repeat (STR) of MICA and HLA-B alleles. RESULTS: The results showed that MICA*A5.1 was significantly associated with TIA (p = .007, odd ratio = 1.958, 95% confidence interval, 1.192-3.214). In addition, high linkage among MICA-129 and six SNPs MICA and HLA-B was detected, and two haplotypes (AAAACAAAAACGGCCTA and AACAAAAAAAACATTAA (p = 5.14E-07 and p = 3.42E-08, respectively)) were significantly associated with TIA. Furthermore, when we analyzed only MICA-129 and HLA-B separately, the haplotypes (AAAACAAAAAA with p = 2.49E-07 and AACAAAAAAAA with p = 2.14E-09) were identified with more significant effects. MICA-129 was completely linked to six SNPs with haplotypes ACATTACA (p = 2.05E-05) significantly associated with TIA. CONCLUSION: These data indicated that there was a significant linkage effect between MICA-129 and other alleles, suggesting that they exert interactive effects as risk factors for the development of TIA.


Assuntos
Agranulocitose , Antitireóideos/efeitos adversos , Adulto , Agranulocitose/induzido quimicamente , China , Feminino , Antígenos HLA-B/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Talanta ; 219: 121170, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887093

RESUMO

A facile strategy for the preparation of nitrogen and phosphorus co-doped carbon dots (N, P-CDs) with long-wavelength emission is attractively proposed in one-pot hydrothermal strategy. The resulting N, P-CDs hold exceptional optical features and display excitation wavelength-independent properties with the emission wavelength at 590 nm, which enable it with the satisfactory relative quantum yield (QY) of 15.6% in long-wavelength region. In addition, the proposed N, P-CDs demonstrates specific selectivity towards ClO- over other competitive reactive oxygen species and exhibits rapid fluorescence response time to ClO-. Moreover, the N, P-CDs exhibits low-cytotoxicity and excellent cell membrane permeability for recognizing ClO- in SMMC-7721 cells, which demonstrates their enormous potential in biological system.


Assuntos
Carbono , Pontos Quânticos , Fluorescência , Nitrogênio , Fósforo , Pontos Quânticos/toxicidade
18.
Cancer Lett ; 495: 112-122, 2020 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-32949679

RESUMO

We hypothesised that synthetic HDL nanoparticles carrying a gemcitabine prodrug and apolipoprotein A-II (sHDLGemA2) would target scavenger receptor-B1 (SR-B1) to preferentially and safely deliver gemcitabine into pancreatic ductal adenocarcinoma (PDAC). We designed, manufactured and characterised sHDLGemA2 nanoparticles sized ~130 nm, incorporating 20 mol% of a gemcitabine prodrug within the lipid bilayer, which strengthens on adding ApoA-II. We measured their ability to inhibit growth in cell lines and cell-derived and patient-derived murine PDAC xenografts. Fluorescent-labelled sHDLGemA2 delivered gemcitabine inside xenografts. Xenograft levels of active gemcitabine after sHDLGemA2 were similar to levels after high-dose free gemcitabine. Growth inhibition in mice receiving 4.5 mg gemcitabine/kg/d, carried in sHDLGemA2, was equivalent to inhibition after high-dose (75 mg/kg/d) free gemcitabine, and greater than inhibition after low-dose (4.5 mg/kg/d) free gemcitabine. sHDLGemA2 slowed growth in semi-resistant cells and a resistant human xenograft. sHDLGemA2 targeted xenografts more effectively than sHDLGemA1. SR-B1 was over-expressed in PDAC cells and xenografts. Targeting by ApoA-II was suppressed by anti-SR-B1. Because sHDLGemA2 provided only ~6% of the free gemcitabine dose for an equivalent response, patient side effects can be greatly reduced, and the sHDLGemA2 concept should be developed through clinical trials.


Assuntos
Apolipoproteína A-II/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Receptores Depuradores Classe B/metabolismo , Animais , Apolipoproteína A-II/química , Apolipoproteína A-II/farmacologia , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Desoxicitidina/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Lipoproteínas HDL/química , Masculino , Camundongos , Nanopartículas , Tamanho da Partícula , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Analyst ; 145(16): 5657-5663, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32638730

RESUMO

Hypoxia in solid tumors is directly linked to the elevated levels of endogenous nitroreductase (NTR). We present a novel fluorescent probe, namely NTNO, for nitroreductase-specific detection based on the NTR-catalyzed reduction of the nitro unit to an amine functionality, and demonstrated its application for hypoxia imaging. NTNO was designed by incorporating a nitro unit as the NTR response site into a benzothiazole derivative. Upon reacting with NTR in the presence of reduced nicotinamide adenine dinucleotide (NADH), the fluorescence of the probe was strongly and sensitively turned on, with a good linearity in the NTR concentration range of 0.5-8.0 µg mL-1 and a detection limit of 48 ng mL-1. Most notably, NTNO has been successfully used for imaging hypoxia levels in living cells, tumor tissues and zebrafish, making it of great potential to monitor NTR in biological systems.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Corantes Fluorescentes/toxicidade , Humanos , Hipóxia , Microscopia de Fluorescência , Nitrorredutases
20.
Chempluschem ; 85(6): 1283-1291, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32543086

RESUMO

Gemcitabine (Gem) is a key drug for pancreatic cancer, yet limited by high systemic toxicity, low bioavailability and poor pharmacokinetic profiles. To overcome these limitations, Gem prodrug amphiphiles were synthesised with oleyl, linoleyl and phytanyl chains. Self-assembly and lyotropic mesophase behaviour of these amphiphiles were examined using polarised optical microscopy and Synchrotron SAXS (SSAXS). Gem-phytanyl was found to form liquid crystalline inverse cubic mesophase. This prodrug was combined with phospholipids and cholesterol to create biomimetic Gem-lipid prodrug nanoparticles (Gem-LPNP), verified by SSAXS and cryo-TEM to form liposomes. In vitro testing of the Gem-LPNP in several pancreatic cancer cell lines showed lower toxicity than Gem. However, in a cell line-derived pancreatic cancer mouse model Gem-LPNP displayed greater tumour growth inhibition than Gem using a fraction (<6 %) of the clinical dose and without any systemic toxicity. The easy production, improved efficacy and low toxicity of Gem-LPNP represents a promising new nanomedicine for pancreatic cancer.


Assuntos
Materiais Biomiméticos/uso terapêutico , Desoxicitidina/análogos & derivados , Nanopartículas/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Animais , Materiais Biomiméticos/química , Carboxilesterase/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/metabolismo , Desoxicitidina/uso terapêutico , Dimiristoilfosfatidilcolina/química , Lipossomos/química , Camundongos Endogâmicos NOD , Camundongos SCID , Nanopartículas/química , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Suínos
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