Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Mais filtros

Base de dados
Intervalo de ano de publicação
Biosens Bioelectron ; 170: 112662, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032198


Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 µL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.

ACS Sens ; 5(8): 2514-2522, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32664724


MicroRNA (MiRNA)-based noninvasive diagnostics are hampered by the challenge in the quantification of circulating miRNAs using a general strategy. Here, we present a base-stacking effect-mediated ultrasensitive electrochemical miRNA sensor (BSee-miR) with a universal sandwich configuration. In the BSee-miR, a short DNA probe (10 nucleotides) self-assembled on a gold electrode surface could effectively capture the target miRNA synergizing with another sequence based on coaxial sandwich base-stacking, which rivals the fully complementary strength. Importantly, such a sandwich structure is flexible to incorporate signal amplification strategies (e.g., biotin-avidin) that are usually difficult to achieve in short sequence detection. Using this design, the BSee-miR achieves a broad dynamic range with a detection limit down to 7.5 fM. Furthermore, we found a high-curvature nanostructuring synergetic base-stacking effect that could improve the sensitivity of the BSee-miR by two orders of magnitude (79.3 aM). Our BSee-miR also has a single-base resolution to discriminate the highly homologous miRNAs. More importantly, this approach is universal and has been used to probe target miRNAs varying in sequences and secondary structures. Our ultrasensitive sensor could detect miRNA in cell lysates and human blood and distinguish cancer patients from normal individuals, promising a versatile tool to measure clinically relevant miRNAs for tumor diagnostics.

J Inorg Biochem ; 209: 111118, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32502875


Near Infrared (NIR) imaging agents are extensively used in the biological or preclinical treatment and diagnosis of a wide range of diseases including cancers and tumors. The current arsenal of NIR compounds are most constituted by organic dyes, polymers, inorganic nanomaterials, whereas Ln molecular complexes explore an alternative approach to design NIR probes that are potentially bring new molecular toolkits into the biomedicine. In this review, NIR imaging agents are categorized according to their molecular sizes, constitution and the key properties and features of each class of compounds are briefly defined wherever possible. To better elucidate the features of Ln complexes, we provide a succinct understanding of sensitization process and molecular Ln luminescence at a mechanistic level, which may help to deliver new insights to design NIR imaging probes. Finally, we used our work on NIR ytterbium (Yb3+) probes as an example to raise awareness of exploring biologically relevant chemical space for lanthanide complexes as chemical entities for biological activity.

Anal Chem ; 92(14): 9877-9886, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32551501


Exosome-associated liquid biopsies are hampered by challenges in the exosomal quantification and phenotyping. Here, we present a bioinspired exosome-activated DNA molecular machine (ExoADM) with multivalent cyclic amplification that enables highly sensitive detection and phenotyping of circulating exosomes. ExoADM harbors two (an exposed and a hidden) DNA toehold domains that actuate sequential branch migration and multivalent recycling in response to exosomal surface markers. Importantly, this self-powered ExoADM achieves a high sensitivity (33 particles/µL) and is compatible with another DNA nanomachine targeting different exosomal surface markers for dual-color phenotyping. Using this strategy, we can simultaneously track the dynamic changes of ExoPD-L1 and ExoCD63 expression induced by signaling molecules. Further, we found that their expression levels on circulating exosomes could well differentiate cancer patients from the normal individuals. More importantly, ExoPD-L1 levels could reflect the efficacy of different treatments and guide anti-PD-1 immunotherapy, suggesting the potential of ExoPD-L1 in clinical diagnosis and targeted therapy monitoring.

Anal Chem ; 91(20): 13198-13205, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31553171


Exosomal microRNAs are essential in intercellular communications and disease progression, yet it remains challenging to quantify the expression level due to their small size and low abundance in blood. Here, we report a "sandwich" electrochemical exosomal microRNA sensor (SEEmiR) to detect target microRNA with high sensitivity and specificity. In SEEmiR, neutrally charged peptide nucleic acid (PNA) enables kinetically favorable hybridization with the microRNA target relative to negatively charged DNA, particularly in a short sequence (10 nt). More importantly, this property allows PNA to cooperate with a spherical nucleic acid (SNA) nanoprobe that heavily loads with oligonucleotide-adsorbed electroactive tags to enhance detection sensitivity and specificity. Such a PNA-microRNA-SNA sandwich construct is able to minimize the background noise via PNA, thereby maximizing the SNA-mediated signal amplification in electrostatic adsorption-based SEEmiR. The synergy between PNA and SNA makes the SEEmiR sensor able to achieve a broad dynamic range (from 100 aM to 1 nM) with a detection limit down to 49 aM (2 orders of magnitude lower than that without SNA) and capable of distinguishing a single-base mismatch. This ultrasensitive sensor provides label-free and enzyme-independent microRNA detection in cell lysates, unpurified tumor exosomal lysates, cancer patients' blood, and accurately differentiates the patients with breast cancer from the healthy ones, suggesting its potential as a promising tool in cancer diagnostics.

Técnicas Eletroquímicas/métodos , Exossomos/química , MicroRNAs/sangue , Ácidos Nucleicos Peptídicos/química , Linhagem Celular Tumoral , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , MicroRNAs/genética , Hibridização de Ácido Nucleico , Ácidos Nucleicos Peptídicos/genética