Abstract
Point-of-care applications rely on biomedical sensors to enable rapid detection with high sensitivity and selectivity. Despite advances in sensor development, there are challenges in cancer diagnostics. Detection of biomarkers, cell receptors, circulating tumor cells, gene identification, and fluorescent tagging are time-consuming due to the sample preparation and response time involved. Here, we present a novel approach to target the enhanced metabolism in breast cancers for rapid detection using fluorescent imaging. Fluorescent analogs of fructose target the fructose-specific transporter GLUT5 in breast cancers and have limited to no response from normal cells. These analogs demonstrate a marked difference in adenocarcinoma and premalignant cells leading to a novel detection approach. The vastly different uptake kinetics of the analogs yields two unique signatures for each cell type. We used normal breast cells MCF10A, adenocarcinoma cells MCF7, and premalignant cells MCF10AneoT, with hepatocellular carcinoma cells HepG2 as the negative control. Our data indicated that MCF10AneoT and MCF7 cells had an observable difference in response to only one of the analogs. The response, observed as fluorescence intensity, leads to a two-point assessment of the cells in any sample. Since the treatment time is 10 min, there is potential for use in rapid on-site high-throughput diagnostics.
Highlights
Point-of-care (POC) and POC-healthcare technologies (POCHT) that monitor changes in the intracellular mechanisms to report disease development have gained prominence in clinical and consumer implementations owing to the ease of access to information, low cost, and self-management of health and wellbeing [1,2,3,4,5]
For the initial uptake analysis, MCF7 cells were treated in a 96-well plate with ManCou probes at different concentrations and the cell fluorescence was measured with a fluorescence plate reader
It is important to note that fructose uptake in the healthy tissues is limited to the liver and intestines, and fructose-specific GLUT5 is upregulated in cancer cells [23,24,30,44,45], supporting our approach to using fructose-based detection
Summary
Point-of-care (POC) and POC-healthcare technologies (POCHT) that monitor changes in the intracellular mechanisms to report disease development have gained prominence in clinical and consumer implementations owing to the ease of access to information, low cost, and self-management of health and wellbeing [1,2,3,4,5]. Biosensors 2018, 8, 39 populations in the heterogeneous environment of the tumor is expected to be based on error-free cancer detection and diagnosis for development of cancer-relevant POC technologies. Within this communication, a metabolism-driven approach for the detection and identification of breast cancers is described. The major efforts in identifying cancer through metabolism changes have focused on targeting glucose uptake and the facilitative glucose transporter GLUT1 [15,16]. We report GLUT5-targeting probes with improved cancer detection based on metabolic profiles. Considering the recognized differences between cells in their metabolic efficiency as well as GLUT5 expression, the probes enable two-point characterization of cells and allow for discrimination of premalignant cells from differentiated epithelial cells and normal cells under an in vitro setting (Figure 1)
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