Facile Strategy To Enhance Specificity and Sensitivity of Molecular Beacons by an Aptamer-Functionalized Delivery Vector

To enhance the specificity and sensitivity of molecular beacons (MBs) in detecting mRNA in living tumor cells, we introduced an aptamer (AS1411) to the delivery system of MBs to form an aptamer-decorated nanoprobe (ANP), which was prepared through self-assembly between AS1411-conjugated carboxymethy...

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Veröffentlicht in:Analytical chemistry (Washington) 2020-01, Vol.92 (2), p.2088-2096
Hauptverfasser: Xu, Chang, He, Xiao-Yan, Peng, Yan, Dai, Bao-Sheng, Liu, Bo-Ya, Cheng, Si-Xue
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container_issue 2
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container_title Analytical chemistry (Washington)
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creator Xu, Chang
He, Xiao-Yan
Peng, Yan
Dai, Bao-Sheng
Liu, Bo-Ya
Cheng, Si-Xue
description To enhance the specificity and sensitivity of molecular beacons (MBs) in detecting mRNA in living tumor cells, we introduced an aptamer (AS1411) to the delivery system of MBs to form an aptamer-decorated nanoprobe (ANP), which was prepared through self-assembly between AS1411-conjugated carboxymethyl chitosan (ACMC) with protamine sulfate (PS)/CaCO3/MB cores. Owing to the specific binding of AS1411 to nucleolin, which is overexpressed in tumor cell membranes and nuclei, an AS1411-decorated MB-delivery system leads to dramatically increased cell uptake of MBs for probing survivin mRNA and thus induces strong intracellular fluorescence emission in targeted tumorous cells and cell nuclei. Furthermore, we demonstrate that ANP can efficiently detect survivin mRNA in mitochondria. In other words, the effective delivery of MBs ensures the precise detection of mRNA distribution in diverse organelles. In addition, we evaluated the efficiency of ANP in probing tumor cells in simulated blood as well as in peripheral blood from a healthy donor and found that the nanoprobe can specifically deliver MBs to tumor cells and identify tumor cells in blood. The targeting delivery system we constructed holds promising applications in precise detection of subcellular distribution of mRNA in living tumor cells as well as in fluorescence-guided cancer detection in liquid biopsy technology. This study provides a facile strategy to effectively improve the specificity and sensitivity of conventional molecular beacons.
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Owing to the specific binding of AS1411 to nucleolin, which is overexpressed in tumor cell membranes and nuclei, an AS1411-decorated MB-delivery system leads to dramatically increased cell uptake of MBs for probing survivin mRNA and thus induces strong intracellular fluorescence emission in targeted tumorous cells and cell nuclei. Furthermore, we demonstrate that ANP can efficiently detect survivin mRNA in mitochondria. In other words, the effective delivery of MBs ensures the precise detection of mRNA distribution in diverse organelles. In addition, we evaluated the efficiency of ANP in probing tumor cells in simulated blood as well as in peripheral blood from a healthy donor and found that the nanoprobe can specifically deliver MBs to tumor cells and identify tumor cells in blood. 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In other words, the effective delivery of MBs ensures the precise detection of mRNA distribution in diverse organelles. In addition, we evaluated the efficiency of ANP in probing tumor cells in simulated blood as well as in peripheral blood from a healthy donor and found that the nanoprobe can specifically deliver MBs to tumor cells and identify tumor cells in blood. The targeting delivery system we constructed holds promising applications in precise detection of subcellular distribution of mRNA in living tumor cells as well as in fluorescence-guided cancer detection in liquid biopsy technology. This study provides a facile strategy to effectively improve the specificity and sensitivity of conventional molecular beacons.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>31855408</pmid><doi>10.1021/acs.analchem.9b04596</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9611-4421</orcidid></addata></record>
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subjects Analytical chemistry
Aptamers
Aptamers, Nucleotide - chemistry
Beacons
Biopsy
Blood
Calcium carbonate
Cell membranes
Chemistry
Chitosan
Chitosan - analogs & derivatives
Chitosan - chemistry
Drug Delivery Systems
Fluorescence
HeLa Cells
Humans
MCF-7 Cells
Membranes
Mitochondria
Molecular Imaging
Molecular Probes - analysis
mRNA
Nuclei
Nuclei (cytology)
Nucleolin
Organelles
Peripheral blood
Protamine sulfate
Self-assembly
Sensitivity enhancement
Survivin
Tumor cells
Tumors
title Facile Strategy To Enhance Specificity and Sensitivity of Molecular Beacons by an Aptamer-Functionalized Delivery Vector
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