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Nanoparticle-enhanced aptamers target cancer cells
Yu-fen huang
Aptamers—the short oligonucleotide aptamer-conjugated gold nanoparticles thor, Yu-Fen Huang of the University strands that can bind specifically to as the basis for colorimetric detection of Florida. The method was inspired by molecular targets, including cell-surof cancer cells. The protocol combines hyperthermia, an anticancer technique face proteins—have shown significant the selectivity of aptamers with greatly based on the principle of using localized promise in molecular-recognition apenhanced sensitivity, thanks to the heat to kill tumor cells selectively while plications. But though the selectivity optical properties of the gold nanoparleaving surrounding, nontargeted cells of aptamers can rival that of unharmed. Huang reasoned antibodies, the binding affinithat an array of conjugated ties and signaling strength are aptamers could be used to deAu–Ag HS nanorod often too weak for practical liver and attach Au–Ag nanoAu–Ag use. In a pair of papers in AC rods directly to cancer cells, Aptamer nanorod (2008, 80, 567–572 and DOI where the nanorods would conjugation 10.1021/ac702037y), Weihong act as efficient photothermal Tan and co-workers at the convectors, absorbing a beam University of Florida and the of IR light and heating to the National Taiwan University point at which they would demonstrate two approaches in destroy the targeted cells. But which conjugated nanopartishe soon found that the techcles can boost aptamer efficacy nique had significant analytiin targeting cancer cells. “We cal advantages as well. have generated many different “On my first trial to test aptamers which can specifically Schematic showing the thiol attachment of aptamers to Au–Ag specific binding efficiency,” recognize target cells,” says nanorods, resulting in cell selection with enhanced signal strength says Huang, “we found that Tan. “But we have to find ways and binding affinities. simultaneous multivalent to make effective use of them.” interactions of multiple apta Both approaches start with a screenticles. “The aptamers are labeled with mers on the carrier played an important ing protocol called cell-SELEX, which gold nanoparticles, and then, because role in binding cell-membrane recepwas developed by Tan’s research group of the binding of the aptamer, the gold tors.” From experiments with Au–Ag to select aptamers that accurately target nanoparticles reach a higher density on nanorods as platforms for up to 80 fluowhole living cells, rather than specific the cell-membrane surface,” says Tan. rophore-labeled aptamers targeted to molecules. The cell-SELEX protocol “And when gold nanoparticles aggregate, cancer cells, Huang and her colleagues generates aptamers that can distinguish you get a much higher absorbance.” ultimately found that binding affinities cancerous cells from normal ones, says From experiments with acute leukeincreased approximately 26-fold comTan, and even differentiate among the mia cells as the target and a lymphoma pared with single aptamers. strains of a particular tumor type. One cell line as control cells, Tan and his coThe improvements immediately sugreason this is possible is that aptamers workers used a thiol linkage to bind 20 gested that the technique could greatly can be selected even though the identinm gold nanoparticles to an aptamer seboost the effectiveness of hyperthermic ties of the specific targets are unknown. quence with high selectivity and affinity treatment. Huang also realized that the Nevertheless, the usefulness of apfor the target cells. The assay was used improved binding affinities, and similar tamer-based probes has been limited successfully for quantitative colorimetry, gains in fluorescence intensity due to so far. Problems include weak binding Tan notes, but also proved so sensitive the density of dye-labeled aptamers on affinities and the fact that many disease that concentrations as low as a few cells each nanorod, would greatly improve cells have only low densities of target per microliter could be detected by the signal strength in flow cytometry and membrane proteins, especially early in naked eye. The assay is simple, effective, molecular-imaging applications as well. disease development when diagnosis can and inexpensive enough to be used for “Especially for cancer cells with very low be most important. The result has been point-of-care detection and diagnosis of density of target membrane proteins,” disappointing sensitivity and low signal various cancers and infectious diseases or says Huang, “our aptamer nanoconjuintensity in flow cytometry and molecu- even for large-scale screening for disease. gates provide an opportunity for highly lar-imaging studies. The other approach (pp 567–572) sensitive recognition of the unique moThat’s where the nanoparticles come has its roots in analysis, diagnostics, lecular signatures of cancer cells.” in. In one paper, Tan and his team used and treatment, says the study’s first au—Thomas Hayden F e b r u a r y 1 , 2 0 0 8 / A n a ly t i c a l C h e m i s t r y
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