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1.
J Control Release ; 354: 196-206, 2023 02.
Article in English | MEDLINE | ID: mdl-36610480

ABSTRACT

Reactive oxygen species (ROS) generation to induce cell death is an effective strategy for cancer therapy. In particular, chemodynamic therapy (CDT), using Fenton-type reactions to generate highly cytotoxic hydroxyl radical (•OH), is a promising treatment modality. However, the therapeutic efficacy of ROS-based cancer treatment is still limited by some critical challenges, such as overexpression of enzymatic and non-enzymatic antioxidants by tumor cells, as well as the low tumor targeting efficiency of therapeutic agents. To address those problems, biomimetic CuZn protoporphyrin IX nanoscale coordination polymers have been developed, which significantly amplify oxidative stress against tumors by simultaneously inhibiting enzymatic and non-enzymatic antioxidants and initiating the CDT. In this design, cancer cell membrane camouflaged nanoparticle exhibits an excellent homotypic targeting effect. After being endocytosed into tumor cells, the nanoparticles induce depletion of the main non-enzymatic antioxidant glutathione (GSH) by undergoing a redox reaction with GSH. Afterward, the redox reaction generated cuprous ion (Cu+) works as a CDT agent for •OH generation. Furthermore, the released Zn protoporphyrin IX strongly inhibits the activity of the typical enzymatic antioxidant heme oxygenase-1. This tetra-modal synergistic strategy endows the biomimetic nanoparticles with great capability for anticancer therapy, which has been demonstrated in both in vitro and in vivo studies.


Subject(s)
Nanoparticles , Neoplasms , Humans , Antioxidants , Reactive Oxygen Species , Glutathione , Oxidative Stress , Biomimetics , Cell Line, Tumor , Hydrogen Peroxide , Tumor Microenvironment
2.
Front Microbiol ; 12: 749783, 2021.
Article in English | MEDLINE | ID: mdl-34803970

ABSTRACT

We developed an ultrafast one-step RT-qPCR assay for SARS-CoV-2 detection, which can be completed in only 30 min on benchtop Bio-Rad CFX96. The assay significantly reduces the running time of conventional RT-qPCR: reduced RT step from 10 to 1 min, and reduced the PCR cycle of denaturation from 10 to 1 s and extension from 30 to 1 s. A cohort of 60 nasopharyngeal swab samples testing showed that the assay had a clinical sensitivity of 100% and a clinical specificity of 100%.

3.
Biomedicines ; 8(12)2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33297544

ABSTRACT

Pancreatic carcinoma (PC) is highly metastatic, and it tends to be detected at advanced stages. Identifying and developing biomarkers for early detection of PC is crucial for a potentially curative treatment. Extracellular vesicles (EVs) are bilayer lipid membrane-structured nanovesicles found in various human bodily fluids, and they play important roles in tumor biogenesis and metastasis. Cancer-derived EVs are enriched with DNA, RNA, protein, and lipid, and they have emerged as attractive diagnostic biomarkers for early detection of PC. In this article, we provided an overview of the cell biology of EVs and their isolation and analysis, and their roles in cancer pathogenesis and progression. Multiplatform analyses of plasma-based exosomes for genomic DNA, micro RNA, mRNA, circular RNA, and protein for diagnosis of PC were critically reviewed. Numerous lines of evidence demonstrate that liquid biopsy with analysis of EV-based biomarkers has variable performance for diagnosis of PC. Future investigation is indicated to optimize the methodology for isolating and analyzing EVs and to identify the combination of EV-based biomarkers and other clinical datasets, with the goal of improving the predictive value, sensitivity, and specificity of screening tests for early detection and diagnosis of PC.

4.
Lab Chip ; 19(14): 2346-2355, 2019 07 09.
Article in English | MEDLINE | ID: mdl-31232418

ABSTRACT

Nanoscale extracellular vesicles (nEVs) have recently demonstrated potential value in cancer diagnostics and treatment monitoring, but translation has been limited by technical challenges in nEV isolation. Thus, we have developed a one-step nEV isolation platform that utilizes nEV size-matched silica nanostructures and a surface-conjugated lipid nanoprobe with an integrated microfluidic mixer. The reported platform has 28.8% capture efficiency from pancreatic cancer plasma and can sufficiently enrich nEVs for simpler positive identification of point mutations, particularly KRAS, in nEV DNA from the plasma of pancreatic cancer patients.


Subject(s)
Extracellular Vesicles/chemistry , Lipids/chemistry , Nanostructures/chemistry , Silicon Dioxide/chemistry , Cell Line, Tumor , Extracellular Vesicles/pathology , Feasibility Studies , Humans , Lab-On-A-Chip Devices , Mutation , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics
5.
Chem Sci ; 6(4): 2166-2171, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-28808523

ABSTRACT

A series of luminescent Ir(iii) complexes were synthesised and evaluated for their ability to act as luminescent G-quadruplex-selective probes. The Ir(iii) complex 9, [Ir(phq)2(phen)]PF6 (where phq = 2-phenylquinoline; phen = 1,10-phenanthroline), exhibited high luminescence in the presence of G-quadruplex DNA compared to dsDNA and ssDNA, and was employed to construct a label-free G-quadruplex-based assay for hepatitis C virus NS3 helicase activity in aqueous solution. Moreover, the application of the assay for screening potential helicase inhibitors was demonstrated. To our knowledge, this is the first G-quadruplex-based assay for helicase activity.

6.
ACS Appl Mater Interfaces ; 6(16): 14008-15, 2014 Aug 27.
Article in English | MEDLINE | ID: mdl-25051997

ABSTRACT

A novel luminescent cyclometalated iridium(III) complex-based chemosensor (1) bearing a zinc-specific receptor, tris(2-pyridylmethyl)amine, and the 3-phenyl-1H-pyrazole ligand has been designed and synthesized. Upon the addition of Zn(2+) ions to a solution of iridium(III) complex 1, a pronounced luminescence color change from blue to green can be observed, which may be attributed to the suppression of photoinduced electron transfer upon complexation of complex 1 with Zn(2+) ions. The interaction of iridium(III) complex 1 with Zn(2+) ions was investigated by UV-vis absorption titration, emission titration, and (1)H NMR titration. Furthermore, the iridium(III) complex 1 exhibited good selectivity for Zn(2+) over 13 other common metal ions, including K(+), Ag(+), Na(+), Ni(2+), Fe(3+), Hg(2+), Cd(2+), Mg(2+), Ca(2+), Cu(2+), Mn(2+), Co(2+), and Pb(2+) ions. The practical application of the iridium(III) complex 1 in visualizing intracellular Zn(2+) distribution in live zebrafish was also demonstrated.


Subject(s)
Ions/metabolism , Iridium/chemistry , Luminescence , Metals/metabolism , Zebrafish/metabolism , Animals
7.
PLoS One ; 9(6): e99930, 2014.
Article in English | MEDLINE | ID: mdl-24927177

ABSTRACT

A novel iridium(III) complex-based chemosensor bearing the 5,6-bis(salicylideneimino)-1,10-phenanthroline ligand receptor was developed, which exhibited a highly sensitive and selective color change from colorless to yellow and a visible turn-off luminescence response upon the addition of Cu(II) ions. The interactions of this iridium(III) complex with Cu2+ ions and thirteen other cations have been investigated by UV-Vis absorption titration, emission titration, and 1H NMR titration.


Subject(s)
Colorimetry/methods , Copper/analysis , Iridium/chemistry , Luminescent Measurements/methods , Copper/chemistry
8.
Chem Commun (Camb) ; 50(40): 5313-5, 2014 May 25.
Article in English | MEDLINE | ID: mdl-24336506

ABSTRACT

A label-free, oligonucleotide-based, switch-on luminescence detection method for T4 polynucleotide kinase activity has been developed using a novel G-quadruplex-selective luminescent Ir(iii) complex probe. The application of the assay for screening potential T4 PNK inhibitors is also demonstrated. To our knowledge, this is the first metal-based assay for PNK activity.


Subject(s)
DNA Probes/chemistry , DNA, Single-Stranded/chemistry , G-Quadruplexes , Iridium/chemistry , Polynucleotide 5'-Hydroxyl-Kinase/metabolism , Biological Assay , Biosensing Techniques , Coordination Complexes/chemistry , Humans , Luminescent Measurements , Phosphorylation
9.
ACS Appl Mater Interfaces ; 5(23): 12249-53, 2013 Dec 11.
Article in English | MEDLINE | ID: mdl-24245499

ABSTRACT

We report herein the synthesis and application of a novel G-quadruplex-selective luminescent iridium(III) complex [Ir(ppy)2(bcp)](+) (where ppy = 2-phenylpyridine and bcp = 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline) for the sensitive detection of apurinic/apyrimidinic (AP) endonuclease activity. Using endonuclease IV (Endo IV) as a model enzyme, a duplex DNA substrate containing a G-quadruplex-forming sequence is cleaved by Endo IV at the abasic site. This releases the G-quadruplex sequence, which folds into a G-quadruplex and is recognised by the G-quadruplex-selective iridium(III) complex with an enhanced luminescence response. The assay achieved high sensitivity and selectivity for Endo IV over other tested enzymes.


Subject(s)
Deoxyribonuclease IV (Phage T4-Induced)/metabolism , G-Quadruplexes , Iridium/chemistry , DNA, Single-Stranded/chemistry , Luminescence
10.
Methods ; 64(3): 218-23, 2013 Dec 15.
Article in English | MEDLINE | ID: mdl-23973810

ABSTRACT

A luminescent iridium(III) complex has been discovered to be selective for G-quadruplex DNA, and was employed in a label-free G-quadruplex-based detection assay for 3'→5' exonuclease activity in aqueous solution. A proof-of-concept of this assay has been demonstrated by using prokaryotic exonuclease III (ExoIII) as a model enzyme. In this assay, a G-quadruplex-forming hairpin oligonucleotide (hairpin-G4 DNA, 5'-GAG3TG4AG3TG4A2GCAGA2G2ATA2CT2C4AC3TC4AC3TC-3') initially exists in a duplex conformation, resulting in a low luminescence signal due to the weak interaction between the iridium(III) complex and duplex DNA. Upon digestion by ExoIII, the guanine-rich sequence is released and folds into a G-quadruplex, which greatly enhances the luminescence emission of the iridium(III) probe. This method was highly sensitive for 3'→5' exonuclease over other DNA-modifying enzymes.


Subject(s)
Biosensing Techniques , Exodeoxyribonucleases/chemistry , Biocatalysis , Coordination Complexes/chemistry , DNA Probes/chemistry , G-Quadruplexes , Inverted Repeat Sequences , Iridium/chemistry , Luminescent Agents/chemistry
11.
Methods ; 64(3): 205-11, 2013 Dec 15.
Article in English | MEDLINE | ID: mdl-23891801

ABSTRACT

A label-free G-quadruplex-based luminescent switch-on assay has been developed for the selective detection of micromolar histidine in aqueous solution. In this study, an iridium(III) complex was employed as a G-quadruplex-specific luminescent probe while a guanine-rich oligonucleotide (Pu27, 5'-TG4AG3TG4AG3TG4A2G2-3')/cupric ion (Cu(2+)) ensemble was employed as a recognition unit for histidine. The initial luminescence of the iridium(III) complex in the presence of G-quadruplex DNA is effectively quenched by Cu(2+) ions due to the Cu(2+)-mediated unfolding of the G-quadruplex motif. The addition of histidine sequesters Cu(2+) ions from the ensemble, thereby restoring the luminescence of the system. The assay could detect down to 1 µM of histidine in aqueous media, and also exhibited good selectivity for histidine over other amino acids with the use of the cysteine, masking agent N-ethylmaleimide. Furthermore, the application of the assay for the detection of histidine in diluted urine samples was demonstrated.


Subject(s)
Biosensing Techniques , Histidine/analysis , Polydeoxyribonucleotides/chemistry , Circular Dichroism , DNA, Single-Stranded/chemistry , G-Quadruplexes , GC Rich Sequence , Luminescent Measurements , Sensitivity and Specificity , Solutions
12.
Methods ; 64(3): 212-7, 2013 Dec 15.
Article in English | MEDLINE | ID: mdl-23876936

ABSTRACT

A parallel G-quadruplex-selective iridium(III) complex has been synthesized and employed as a luminescent probe in a label-free G-quadruplex-based detection assay for Ca(2+) ions in aqueous solution. In this assay, a guanine-rich oligonucleotide (G4, 5'-G4T4G4-3') initially exists in an antiparallel G-quadruplex conformation, resulting in a low luminescence signal. Upon incubation with Ca(2+) ions, the antiparallel G-quadruplex is induced into a parallel G-quadruplex conformation, which greatly enhances the luminescence emission of the iridium(III) probe. This method was highly sensitive for Ca(2+) ions with a limit of detection in the nanomolar range, and was selective for Ca(2+) over other metal ions.


Subject(s)
Biosensing Techniques , Calcium/analysis , Polydeoxyribonucleotides/chemistry , Calcium/chemistry , Coordination Complexes/analysis , Coordination Complexes/chemistry , DNA/chemistry , DNA, Single-Stranded/chemistry , G-Quadruplexes , Limit of Detection , Luminescent Agents/chemistry , Luminescent Measurements
13.
Angew Chem Int Ed Engl ; 52(30): 7666-82, 2013 Jul 22.
Article in English | MEDLINE | ID: mdl-23765907

ABSTRACT

The serendipitous discovery of the anticancer drug cisplatin cemented medicinal inorganic chemistry as an independent discipline in the 1960s. Luminescent metal complexes have subsequently been widely applied for sensing, bio-imaging, and in organic light-emitting diode applications. Transition-metal complexes possess a variety of advantages that make them suitable as therapeutics and as luminescent probes for biomolecules. It is thus highly desirable to develop new luminescent metal complexes that either interact with DNA through different binding modes or target alternative cellular machinery such as proteins as well as to provide a more effective means of monitoring disease progression. In this Review, we highlight recent examples of biologically active luminescent metal complexes that can target and probe a specific biomolecule, and offer insights into the future potential of these compounds for the investigation and treatment of human diseases.


Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/chemistry , Luminescent Agents/chemistry , Luminescent Measurements/methods , Metals/chemistry , Antineoplastic Agents/chemistry , Drug Design , Humans , Luminescent Agents/therapeutic use , Metals/metabolism
14.
Angew Chem Int Ed Engl ; 52(30): 7742-6, 2013 Jul 22.
Article in English | MEDLINE | ID: mdl-23775868

ABSTRACT

Peaceful coexistence: A double quadruplex composed of an i-motif and a G-quadruplex was constructed within one oligonucleotide strand (see picture). The defined double-quadruplex structure can serve as a NOTIF logic gate on the basis of the fluorescence of crystal violet.


Subject(s)
G-Quadruplexes , Oligonucleotides/chemistry , Circular Dichroism , Nucleic Acid Conformation , Spectrometry, Fluorescence
15.
Methods ; 64(3): 224-8, 2013 Dec 15.
Article in English | MEDLINE | ID: mdl-23748144

ABSTRACT

We report herein a luminescent switch-on label-free G-quadruplex-based assay for the rapid and sensitive detection of polymerase proofreading activity using a novel iridium(III) complex as a G-quadruplex-selective probe. The interaction of the iridium(III) complex with the G-quadruplex motif facilitates the highly sensitive switch-on detection of polymerase proofreading activity. Using T4 DNA polymerase (T4 pol) as a model enzyme, the assay achieved high sensitivity and selectivity for T4 pol over other tested enzymes.


Subject(s)
Coordination Complexes/chemistry , DNA-Directed DNA Polymerase/chemistry , Enzyme Assays , Luminescent Agents/chemistry , Base Sequence , Biosensing Techniques , DNA Probes/chemistry , DNA, Single-Stranded/chemistry , Exonucleases/chemistry , G-Quadruplexes , Iridium/chemistry , Luminescent Measurements , Molecular Sequence Data , Polymerase Chain Reaction , Sensitivity and Specificity
16.
Chem Commun (Camb) ; 49(50): 5630-2, 2013 Jun 25.
Article in English | MEDLINE | ID: mdl-23559154

ABSTRACT

We report herein a simple and convenient luminescent assay for detection of base excision repair enzyme activity using an Ir(III) complex as a G-quadruplex selective probe. Using uracil-DNA glycosylase (UDG) as a model enzyme, the assay achieved high sensitivity and selectivity for UDG over other tested enzymes. The utility of the assay for screening potential UDG inhibitors was also demonstrated.


Subject(s)
G-Quadruplexes , Uracil-DNA Glycosidase/metabolism , Biological Assay , Biosensing Techniques , Coordination Complexes/chemistry , DNA Repair , Iridium/chemistry , Luminescence , Luminescent Measurements , Molecular Probe Techniques , Uracil-DNA Glycosidase/antagonists & inhibitors , Uracil-DNA Glycosidase/chemistry
17.
Nucleic Acids Res ; 41(8): 4345-59, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23435319

ABSTRACT

G-quadruplexes represent a versatile sensing platform for the construction of label-free molecular detection assays owing to their diverse structures that can be selectively recognized by G-quadruplex-specific luminescent probes. In this Survey and Summary, we highlight recent examples of the application of the label-free strategy for the development of G-quadruplex-based luminescent detection platforms with a view towards the potential application of tetraplex structures in the design of DNA logic gates.


Subject(s)
Computers, Molecular , G-Quadruplexes , Luminescent Agents , Aptamers, Nucleotide , DNA/analysis , Enzymes/analysis , Luminescent Agents/chemistry , Metals/analysis , Sulfhydryl Compounds/analysis
18.
Chem Soc Rev ; 42(8): 3427-40, 2013 Apr 21.
Article in English | MEDLINE | ID: mdl-23348604

ABSTRACT

Breakthrough advances in chemistry and biology over the last two decades have vastly expanded the repertoire of nucleic acid structure and function with potential application in multiple areas of science and technology, including sensing and analytical applications. DNA oligonucleotides represent popular tools for the development of sensing platforms due to their low cost, rich structural polymorphism, and their ability to bind to cognate ligands with sensitivity and specificity rivaling those for protein enzymes and antibodies. In this review, we give an overview of the "label-free" approach that has been a particular focus of our group and others for the construction of luminescent DNA-based sensing platforms. The label-free strategy aims to overcome some of the drawbacks associated with the use of covalently-labeled oligonucleotides prevalent in electrochemical and optical platforms. Label-free DNA-based probes harness the selective interaction between luminescent dyes and functional oligonucleotides that exhibit a "structure-switching" response upon binding to analytes. Based on the numerous examples of label-free luminescent DNA-based probes reported recently, we envisage that this field would continue to thrive and mature in the years to come.


Subject(s)
Luminescent Agents/chemistry , Oligonucleotide Probes/chemistry , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/metabolism , Biosensing Techniques , DNA/analysis , Deoxyribonucleases/metabolism , Humans , Metals/analysis , Oligonucleotide Probes/metabolism , Ribonucleases/metabolism
19.
Biosens Bioelectron ; 41: 871-4, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23040875

ABSTRACT

A label-free oligonucleotide-based luminescent switch-on assay has been developed for the selective detection of sub-nanomolar Pb(2+) ions in aqueous solution and real water samples. An iridium(III) complex was employed as a G-quadruplex specific luminescent probe and a guanine rich DNA (PS2.M, 5'-GTG(3)TAG(3)CG(3)T(2)G(2)-3') was employed as recognition unit for Pb(2+) ions. The PS2.M exists in a single-stranded conformation in the absence of Pb(2+) ions, and the weak binding of the iridium(III) probe to ssDNA results in a weak luminescence signal. Upon binding to Pb(2+) ions, the single-stranded DNA sequence (PS2.M) is induced into a G-quadruplex conformation, which greatly enhances the luminescence emission of the iridium(III) probe. The assay can detect Pb(2+) ions in aqueous media with a limit of detection of 600 pM. It also exhibits good selectivity for Pb(2+) ions over other heavy metal ions. Furthermore, the application of the assay for the detection of Pb(2+) ions in spiked river water samples has been demonstrated.


Subject(s)
Biosensing Techniques/instrumentation , Lead/analysis , Luminescent Measurements/instrumentation , Microchemistry/instrumentation , Molecular Probe Techniques/instrumentation , Rivers/chemistry , Water Pollutants, Chemical/analysis , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity , Solutions , Staining and Labeling , Water/chemistry
20.
Chem Commun (Camb) ; 49(8): 771-3, 2013 Jan 28.
Article in English | MEDLINE | ID: mdl-23192322

ABSTRACT

A G-quadruplex-selective luminescent iridium(III) switch-on probe has been developed for the detection of cysteine (Cys) in aqueous solution. The system is highly sensitive and selective towards Cys with a tunable range of detection. The detection of glutathione (GSH) is also examined.


Subject(s)
Cysteine/analysis , DNA/chemistry , G-Quadruplexes , Glutathione/analysis , Iridium/chemistry , Luminescent Agents/chemistry , Coordination Complexes/chemistry , Luminescent Measurements/methods , Sensitivity and Specificity
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