A multichannel nanosensor for instantaneous readout of cancer drug mechanisms

• Published in: Nature nanotechnology Vol. 10; no. 1; pp. 65 - 69
• Main Authors: Rana, Subinoy, Le, Ngoc D. B., Mout, Rubul, Saha, Krishnendu, Tonga, Gulen Yesilbag, Bain, Robert E. S., Miranda, Oscar R., Rotello, Caren M., Rotello, Vincent M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2015; Nature Publishing Group
• Subjects: 631/61/350/354; 639/925/927/356; Animals; Antineoplastic Agents - administration & dosage; Biological Assay - instrumentation; Cell Line, Tumor; Drug Monitoring - instrumentation; Drugs; Equipment Design; Equipment Failure Analysis; Fluorescence; Gold; letter; Materials Science; Mice; Multichannel; Nanostructure; Nanotechnology; Nanotechnology - instrumentation; Nanotechnology and Microengineering; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Proteins; Reproducibility of Results; Sensitivity and Specificity; Sensors; Signatures; Spectrometry, Fluorescence - instrumentation; Toxicology
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/nnano.2014.285

A high-throughput nanosensor based on a gold nanoparticle and fluorescent proteins allows mechanisms of chemotherapeutic drugs to be screened in minutes, offering a tool for expediting research in drug discovery and toxicology. Screening methods that use traditional genomic 1 , 2 , 3 , transcriptional 4 , proteomic 5 , 6 and metabonomic 7 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 8 , 9 , 10 . 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.