Detection of GNAQ mutations and reduction of cell viability in uveal melanoma cells with functionalized gold nanoparticles

Verfasser / Beitragende:
[Christian Posch, Alfonso Latorre, Michelle Crosby, Anna Celli, Ana Latorre, Igor Vujic, Martina Sanlorenzo, Gary Green, Jingly Weier, Mitchell Zekhtser, Jeffrey Ma, Gabriela Monico, Devron Char, Denis Jusufbegovic, Klemens Rappersberger, Álvaro Somoza, Susana Ortiz-Urda]
Ort, Verlag, Jahr:
2015
Enthalten in:
Biomedical Microdevices, 17/1(2015-02-01), 1-9
Format:
Artikel (online)
ID: 605479291
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024 7 0 |a 10.1007/s10544-014-9908-7  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s10544-014-9908-7 
245 0 0 |a Detection of GNAQ mutations and reduction of cell viability in uveal melanoma cells with functionalized gold nanoparticles  |h [Elektronische Daten]  |c [Christian Posch, Alfonso Latorre, Michelle Crosby, Anna Celli, Ana Latorre, Igor Vujic, Martina Sanlorenzo, Gary Green, Jingly Weier, Mitchell Zekhtser, Jeffrey Ma, Gabriela Monico, Devron Char, Denis Jusufbegovic, Klemens Rappersberger, Álvaro Somoza, Susana Ortiz-Urda] 
520 3 |a Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Early treatment may improve any chances of preventing metastatic disease, but diagnosis of small UM is challenging. Up to 95% of all UMs carry somatic mutations in the G-coupled proteins GNAQ and GNA11 promoting anchorage-independent growth and proliferation. About 50% of UMs are fatal. Once metastatic, patients have limited options for successful therapy. Methods: We have developed functionalized gold nanoparticles (AuNPs) to visualize transcripts of mutant GNAQ mRNA in living cells. In addition to their suitability as a specific tool for GNAQ mutation detection, we have developed a novel linker that enables conjugation of siRNAs to AuNPs allowing for greater and more rapid intracellular release of siRNAs compared to previously described approaches. Results: Binding of modified AuNPs to matching target mRNA leads to conformational changes, resulting in a detectable fluorescent signal that can be used for mutation detection in living cells. Knockdown of GNAQ with siRNA-AuNPs effectively reduced downstream signals and decreased cell viability in GNAQ mutant uveal melanoma cells. Conclusion: AuNPs may in future be developed to serve as sensors for mutations of vital importance. The new release system for siRNA-AuNP improves previous systems, which conceivably will be useful for future therapeutic gene regulatory approaches. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a siRNA  |2 nationallicence 
690 7 |a GNAQ  |2 nationallicence 
690 7 |a Fluorescence  |2 nationallicence 
690 7 |a Treatment  |2 nationallicence 
690 7 |a Linker  |2 nationallicence 
700 1 |a Posch  |D Christian  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Latorre  |D Alfonso  |u Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), & CNB-CSIC-IMDEA Nanociencia Associated Unit "Unidad de Nanobiotecnología”, 28049, Madrid, Spain  |4 aut 
700 1 |a Crosby  |D Michelle  |u North County Eye Surgery Associates, 320 Santa Fe Drive Suite 104, 92024, Encinitas, USA  |4 aut 
700 1 |a Celli  |D Anna  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Latorre  |D Ana  |u Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), & CNB-CSIC-IMDEA Nanociencia Associated Unit "Unidad de Nanobiotecnología”, 28049, Madrid, Spain  |4 aut 
700 1 |a Vujic  |D Igor  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Sanlorenzo  |D Martina  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Green  |D Gary  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Weier  |D Jingly  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Zekhtser  |D Mitchell  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Ma  |D Jeffrey  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Monico  |D Gabriela  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
700 1 |a Char  |D Devron  |u Departments of Ophthalmology, Stanford University, University of California San Francisco and California Pacific Medical Center, 45 Castro Street, 94114, San Francisco, USA  |4 aut 
700 1 |a Jusufbegovic  |D Denis  |u Departments of Ophthalmology, Stanford University, University of California San Francisco and California Pacific Medical Center, 45 Castro Street, 94114, San Francisco, USA  |4 aut 
700 1 |a Rappersberger  |D Klemens  |u Department of Dermatology, The Rudolfstiftung Hospital, Juchgasse 25, 1030, Vienna, Austria  |4 aut 
700 1 |a Somoza  |D Álvaro  |u Department of Dermatology, The Rudolfstiftung Hospital, Juchgasse 25, 1030, Vienna, Austria  |4 aut 
700 1 |a Ortiz-Urda  |D Susana  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
773 0 |t Biomedical Microdevices  |d Springer US; http://www.springer-ny.com  |g 17/1(2015-02-01), 1-9  |x 1387-2176  |q 17:1<1  |1 2015  |2 17  |o 10544 
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950 |B NATIONALLICENCE  |P 700  |E 1-  |a Posch  |D Christian  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Latorre  |D Alfonso  |u Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), & CNB-CSIC-IMDEA Nanociencia Associated Unit "Unidad de Nanobiotecnología”, 28049, Madrid, Spain  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Crosby  |D Michelle  |u North County Eye Surgery Associates, 320 Santa Fe Drive Suite 104, 92024, Encinitas, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Celli  |D Anna  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Latorre  |D Ana  |u Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), & CNB-CSIC-IMDEA Nanociencia Associated Unit "Unidad de Nanobiotecnología”, 28049, Madrid, Spain  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Vujic  |D Igor  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sanlorenzo  |D Martina  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Green  |D Gary  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Weier  |D Jingly  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zekhtser  |D Mitchell  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ma  |D Jeffrey  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Monico  |D Gabriela  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Char  |D Devron  |u Departments of Ophthalmology, Stanford University, University of California San Francisco and California Pacific Medical Center, 45 Castro Street, 94114, San Francisco, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Jusufbegovic  |D Denis  |u Departments of Ophthalmology, Stanford University, University of California San Francisco and California Pacific Medical Center, 45 Castro Street, 94114, San Francisco, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Rappersberger  |D Klemens  |u Department of Dermatology, The Rudolfstiftung Hospital, Juchgasse 25, 1030, Vienna, Austria  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Somoza  |D Álvaro  |u Department of Dermatology, The Rudolfstiftung Hospital, Juchgasse 25, 1030, Vienna, Austria  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ortiz-Urda  |D Susana  |u Department of Dermatology, Mount Zion Cancer Research Center, University of California San Francisco, 2340 Sutter Street N461, 94115, San Francisco, CA, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Biomedical Microdevices  |d Springer US; http://www.springer-ny.com  |g 17/1(2015-02-01), 1-9  |x 1387-2176  |q 17:1<1  |1 2015  |2 17  |o 10544