RESUMO
We report a polymer-based sensor that rapidly detects cancer based on changes in serum protein levels. Using three ratiometric fluorescence outputs, this simple system identifies early stage and metastatic lung cancer with a high level of accuracy exceeding many biomarker-based assays, making it an attractive strategy for point-of-care testing.
Assuntos
Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Corantes Fluorescentes/química , Neoplasias Pulmonares/diagnóstico por imagem , Polímeros/química , Animais , Fluorescência , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Neoplasias Experimentais/sangue , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/secundário , Testes ImediatosRESUMO
Endocrine disrupting chemicals (EDCs) interact with estrogen receptors (ERs), causing a broad range of adverse health effects. Current assays for EDC activity are slow and often lack sensitivity. We report here an ultra-sensitive nanosensor that can detect estrogenic cellular changes in ER(+) MCF-7 cells rapidly (minutes) at several orders of magnitude lower than the generally used assays. Notably, the sensor responses at these ultra-low EDC levels correlated with an increased synthesis phase (S-phase) cell population of EDC-treated cells. The nanosensor was also able to detect binary EDC mixture effects, with synergism observed for bisphenol A (BPA) - 17ß-estradiol (E2), and antagonism for dicyclohexylphthalate (DCHP) - E2 and benzo(a)pyrene (BaP) - E2.
Assuntos
Disruptores Endócrinos/análise , Estrogênios não Esteroides/análise , Proteínas de Fluorescência Verde/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Antagonismo de Drogas , Sinergismo Farmacológico , Disruptores Endócrinos/farmacologia , Estradiol/análise , Estradiol/farmacologia , Estrogênios não Esteroides/farmacologia , Ouro/química , Humanos , Células MCF-7 , Fase S/efeitos dos fármacosRESUMO
We report a nanosensor that uses cell lysates to rapidly profile the tumorigenicity of cancer cells. This sensing platform uses host-guest interactions between cucurbit[7]uril and the cationic headgroup of a gold nanoparticle to non-covalently modify the binding of three fluorescent proteins of a multi-channel sensor in situ. This approach doubles the number of output channels to six, providing single-well identification of cell lysates with 100% accuracy. Significantly, this classification could be extended beyond the training set, determining the invasiveness of novel cell lines. The unique fingerprint of these cell lysates required minimal sample quantity (200 ng, â¼1000 cells), making the methodology compatible with microbiopsy technology.
Assuntos
Técnicas Biossensoriais , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Proteínas Luminescentes/química , Nanopartículas Metálicas/química , Nanotecnologia , Neoplasias/patologia , Sítios de Ligação , Linhagem Celular Tumoral , Ouro/química , Humanos , Estrutura Molecular , Neoplasias/diagnóstico por imagemRESUMO
Screening methods that use traditional genomic, transcriptional, proteomic and metabonomic signatures to characterize drug mechanisms are known. However, they are time consuming and require specialized equipment. Here, we present a high-throughput multichannel sensor platform that can profile the mechanisms of various chemotherapeutic drugs in minutes. The sensor consists of a gold nanoparticle complexed with three different fluorescent proteins that can sense drug-induced physicochemical changes on cell surfaces. In the presence of cells, fluorescent proteins are rapidly displaced from the gold nanoparticle surface and fluorescence is restored. Fluorescence 'turn on' of the fluorescent proteins depends on the drug-induced cell surface changes, generating patterns that identify specific mechanisms of cell death induced by drugs. The nanosensor is generalizable to different cell types and does not require processing steps before analysis, offering an effective way to expedite research in drug discovery, toxicology and cell-based sensing.
Assuntos
Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/instrumentação , Nanotecnologia/instrumentação , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Espectrometria de Fluorescência/instrumentação , Animais , Bioensaio/instrumentação , Linhagem Celular Tumoral , Desenho de Equipamento , Análise de Falha de Equipamento , Camundongos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Array-based sensing using nanoparticles (NPs) provides an attractive alternative to specific biomarker-focused strategies for cancer diagnosis. The physical and chemical properties of NPs provide both the recognition and transduction capabilities required for biosensing. Array-based sensors utilize a combined response from the interactions between sensors and analytes to generate a distinct pattern (fingerprint) for each analyte. These interactions can be the result of either the combination of multiple specific biomarker recognition (specific binding) or multiple selective binding responses, known as chemical nose sensing. The versatility of the latter array-based sensing using NPs can facilitate the development of new personalized diagnostic methodologies in cancer diagnostics, a necessary evolution in the current healthcare system to better provide personalized treatments. This review will describe the basic principle of array-based sensors, along with providing examples of both invasive and noninvasive samples used in cancer diagnosis.
Assuntos
Biomarcadores Tumorais/análise , Técnicas de Diagnóstico Molecular/métodos , Nanopartículas , Neoplasias/química , Neoplasias/diagnóstico , Análise Serial de Tecidos/métodos , HumanosRESUMO
Getting out is just as important for nano-therapeutics as getting in. Exocytosis rates determine residency time in the cell, an important determinant for therapeutic efficacy and also for eventual clearance from the cell. In this study, it is shown that exocytosis efficiency is determined by surface functionality, providing a strategy for optimizing nanocarriers.