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 |
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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. |
doi_str_mv | 10.1021/acs.analchem.9b04596 |
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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. 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.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.9b04596</identifier><identifier>PMID: 31855408</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>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</subject><ispartof>Analytical chemistry (Washington), 2020-01, Vol.92 (2), p.2088-2096</ispartof><rights>Copyright American Chemical Society Jan 21, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a291t-6fa381aaa3f899754518f2871bed0d0b6c0f169d139e041bcbbc3b9e937b463d3</citedby><cites>FETCH-LOGICAL-a291t-6fa381aaa3f899754518f2871bed0d0b6c0f169d139e041bcbbc3b9e937b463d3</cites><orcidid>0000-0001-9611-4421</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.9b04596$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.9b04596$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31855408$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Chang</creatorcontrib><creatorcontrib>He, Xiao-Yan</creatorcontrib><creatorcontrib>Peng, Yan</creatorcontrib><creatorcontrib>Dai, Bao-Sheng</creatorcontrib><creatorcontrib>Liu, Bo-Ya</creatorcontrib><creatorcontrib>Cheng, Si-Xue</creatorcontrib><title>Facile Strategy To Enhance Specificity and Sensitivity of Molecular Beacons by an Aptamer-Functionalized Delivery Vector</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><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.</description><subject>Analytical chemistry</subject><subject>Aptamers</subject><subject>Aptamers, Nucleotide - chemistry</subject><subject>Beacons</subject><subject>Biopsy</subject><subject>Blood</subject><subject>Calcium carbonate</subject><subject>Cell membranes</subject><subject>Chemistry</subject><subject>Chitosan</subject><subject>Chitosan - analogs & derivatives</subject><subject>Chitosan - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Fluorescence</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>MCF-7 Cells</subject><subject>Membranes</subject><subject>Mitochondria</subject><subject>Molecular Imaging</subject><subject>Molecular Probes - analysis</subject><subject>mRNA</subject><subject>Nuclei</subject><subject>Nuclei (cytology)</subject><subject>Nucleolin</subject><subject>Organelles</subject><subject>Peripheral blood</subject><subject>Protamine sulfate</subject><subject>Self-assembly</subject><subject>Sensitivity enhancement</subject><subject>Survivin</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi1ERZeWf4CQJS5csow_4sTHUrqA1KqHFq6R7UyoqyRebKfq9teTaLc9cOBkjfW874z0EPKewZoBZ5-NS2szmt7d4bDWFmSp1SuyYiWHQtU1f01WACAKXgEck7cp3QMwBky9IceC1WUpoV6Rx41xvkd6k6PJ-HtHbwO9GO_M6Oa_LTrfeefzjpqxpTc4Jp_9wzKHjl6FHt3Um0i_oHFhTNQuHD3bZjNgLDbT6LIP84n-CVv6FXv_gHFHf6HLIZ6So870Cd8d3hPyc3Nxe_69uLz-9uP87LIwXLNcqM6ImhljRFdrXZWyZHXH64pZbKEFqxx0TOmWCY0gmXXWOmE1alFZqUQrTsinfe82hj8TptwMPjnsezNimFLDBdeV4KDLGf34D3ofpjjfv1BSSqVYxWdK7ikXQ0oRu2Yb_WDirmHQLGaa2UzzbKY5mJljHw7lkx2wfQk9q5gB2ANL_GXxfzv_As-nnig</recordid><startdate>20200121</startdate><enddate>20200121</enddate><creator>Xu, Chang</creator><creator>He, Xiao-Yan</creator><creator>Peng, Yan</creator><creator>Dai, Bao-Sheng</creator><creator>Liu, Bo-Ya</creator><creator>Cheng, Si-Xue</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9611-4421</orcidid></search><sort><creationdate>20200121</creationdate><title>Facile Strategy To Enhance Specificity and Sensitivity of Molecular Beacons by an Aptamer-Functionalized Delivery Vector</title><author>Xu, Chang ; He, Xiao-Yan ; Peng, Yan ; Dai, Bao-Sheng ; Liu, Bo-Ya ; Cheng, Si-Xue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a291t-6fa381aaa3f899754518f2871bed0d0b6c0f169d139e041bcbbc3b9e937b463d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analytical chemistry</topic><topic>Aptamers</topic><topic>Aptamers, Nucleotide - chemistry</topic><topic>Beacons</topic><topic>Biopsy</topic><topic>Blood</topic><topic>Calcium carbonate</topic><topic>Cell membranes</topic><topic>Chemistry</topic><topic>Chitosan</topic><topic>Chitosan - analogs & derivatives</topic><topic>Chitosan - chemistry</topic><topic>Drug Delivery Systems</topic><topic>Fluorescence</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>MCF-7 Cells</topic><topic>Membranes</topic><topic>Mitochondria</topic><topic>Molecular Imaging</topic><topic>Molecular Probes - analysis</topic><topic>mRNA</topic><topic>Nuclei</topic><topic>Nuclei (cytology)</topic><topic>Nucleolin</topic><topic>Organelles</topic><topic>Peripheral blood</topic><topic>Protamine sulfate</topic><topic>Self-assembly</topic><topic>Sensitivity enhancement</topic><topic>Survivin</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Chang</creatorcontrib><creatorcontrib>He, Xiao-Yan</creatorcontrib><creatorcontrib>Peng, Yan</creatorcontrib><creatorcontrib>Dai, Bao-Sheng</creatorcontrib><creatorcontrib>Liu, Bo-Ya</creatorcontrib><creatorcontrib>Cheng, Si-Xue</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Chang</au><au>He, Xiao-Yan</au><au>Peng, Yan</au><au>Dai, Bao-Sheng</au><au>Liu, Bo-Ya</au><au>Cheng, Si-Xue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Facile Strategy To Enhance Specificity and Sensitivity of Molecular Beacons by an Aptamer-Functionalized Delivery Vector</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2020-01-21</date><risdate>2020</risdate><volume>92</volume><issue>2</issue><spage>2088</spage><epage>2096</epage><pages>2088-2096</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>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.</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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